Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

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Reedijk Jan

2008-06-01

Full Text Available Abstract Background Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated. Methods Sub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of Results In the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance. Conclusion Our results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours

Protein (Viridiplantae): 356536840 [PGDBj - Ortholog DB

Lifescience Database Archive (English)

Full Text Available 24:2780 3398:2780 71240:414 91827:414 71275:1623 91835:562 72025:981 3803:981 3814:981 163735:1026 3846:1026 3847:1026 PREDICTED: pat...ellin-4-like Glycine max MNNTNECCCNDENGKIVVGVPLVFNFFDKNTNNIEKSLKVQLEKKNQLEDHDCDQEDD

Protein (Viridiplantae): 356543245 [PGDBj - Ortholog DB

Lifescience Database Archive (English)

Full Text Available 24:2780 3398:2780 71240:414 91827:414 71275:1623 91835:562 72025:981 3803:981 3814:981 163735:1026 3846:1026 3847:1026 PREDICTED: pat...ellin-3-like Glycine max MAQNDSNPTPPPEPHVAAEPITEDLVQDKEEEDDSSKIVIPVPESESLSLKEDSNRVS

Protein (Viridiplantae): 356506815 [PGDBj - Ortholog DB

Lifescience Database Archive (English)

Full Text Available 24:2780 3398:2780 71240:414 91827:414 71275:1623 91835:562 72025:981 3803:981 3814:981 163735:1026 3846:1026 3847:1026 PREDICTED: pat...ellin-6-like Glycine max MMDTTSSPLSLQTQKTTFQELPEASPKPYKKGIVATLMGGGLFKEDNYFVSLLRSSEK

Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.

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Dimitra T Stefanou

Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780 and one resistant (A2780/C30 to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs from OC patients, sensitive (n = 7 or resistant (n = 4 to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9 were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05. Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03. Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05. We conclude

Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer

LENUS (Irish Health Repository)

Ehlen, Asa

2010-08-20

Abstract Background We recently demonstrated that increased expression of the RNA-binding protein RBM3 is associated with a favourable prognosis in breast cancer. The aim of this study was to examine the prognostic value of RBM3 mRNA and protein expression in epithelial ovarian cancer (EOC) and the cisplatin response upon RBM3 depletion in a cisplatin-sensitive ovarian cancer cell line. Methods RBM3 mRNA expression was analysed in tumors from a cohort of 267 EOC cases (Cohort I) and RBM3 protein expression was analysed using immunohistochemistry (IHC) in an independent cohort of 154 prospectively collected EOC cases (Cohort II). Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS). Immunoblotting and IHC were used to examine the expression of RBM3 in a cisplatin-resistant ovarian cancer cell line A2780-Cp70 and its cisplatin-responsive parental cell line A2780. The impact of RBM3 on cisplatin response in EOC was assessed using siRNA-mediated silencing of RBM3 in A2780 cells followed by cell viability assay and cell cycle analysis. Results Increased RBM3 mRNA expression was associated with a prolonged RFS (HR = 0.64, 95% CI = 0.47-0.86, p = 0.003) and OS (HR = 0.64, 95% CI = 0.44-0.95, p = 0.024) in Cohort I. Multivariate analysis confirmed that RBM3 mRNA expression was an independent predictor of a prolonged RFS, (HR = 0.61, 95% CI = 0.44-0.84, p = 0.003) and OS (HR = 0.62, 95% CI = 0.41-0.95; p = 0.028) in Cohort I. In Cohort II, RBM3 protein expression was associated with a prolonged OS (HR = 0.53, 95% CI = 0.35-0.79, p = 0.002) confirmed by multivariate analysis (HR = 0.61, 95% CI = 0.40-0.92, p = 0.017). RBM3 mRNA and protein expression levels were significantly higher in the cisplatin sensitive A2780 cell line compared to the cisplatin resistant A2780-Cp70 derivative. siRNA-mediated silencing of RBM3 expression in the A2780 cells resulted

Enhanced Cytotoxicity of Folic Acid-Targeted Liposomes Co-Loaded with C6 Ceramide and Doxorubicin: In Vitro Evaluation on HeLa, A2780-ADR, and H69-AR Cells.

Science.gov (United States)

Sriraman, Shravan Kumar; Pan, Jiayi; Sarisozen, Can; Luther, Ed; Torchilin, Vladimir

2016-02-01

Current research in cancer therapy is beginning to shift toward the use of combinational drug treatment regimens. However, the efficient delivery of drug combinations is governed by a number of complex factors in the clinical setting. Therefore, the ability to synchronize the pharmacokinetics of the individual therapeutic agents present in combination not only to allow for simultaneous tumor accumulation but also to allow for a synergistic relationship at the intracellular level could prove to be advantageous. In this work, we report the development of a novel folic acid-targeted liposomal formulation simultaneously co-loaded with C6 ceramide and doxorubicin [FA-(C6+Dox)-LP]. In vitro cytotoxicity assays showed that the FA-(C6+Dox)-LP was able to significantly reduce the IC50 of Dox when compared to that after the treatment with the doxorubicin-loaded liposomes (Dox-LP) as well as the untargeted drug co-loaded (C6+Dox)-LP on HeLa, A2780-ADR, and H69-AR cells. The analysis of the cell cycle distribution showed that while the C6 liposomes (C6-LP) did not cause cell cycle arrest, all the Dox-containing liposomes mediated cell cycle arrest in HeLa cells in the G2 phase at Dox concentrations of 0.3 and 1 μM and in the S phase at the higher concentrations. It was also found that this arrest in the S phase precedes the progression of the cells to apoptosis. The targeted FA-(C6+Dox)-LP were able to significantly enhance the induction of apoptotic events in HeLa cell monolayers as compared to the other treatment groups. Next, using time-lapse phase holographic imaging microscopy, it was found that upon treatment with the FA-(C6+Dox)-LP, the HeLa cells underwent rapid progression to apoptosis after 21 h as evidenced by a drastic drop in the average area of the cells after loss of cell membrane integrity. Finally, upon evaluation in a HeLa spheroid cell model, treatment with the FA-(C6+Dox)-LP showed significantly higher levels of cell death compared to those with C6-LP and

Discovery of imidazo[1,2- a ]-pyridine inhibitors of pan-PI3 kinases that are efficacious in a mouse xenograft model

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Han, Wooseok; Menezes, Daniel L.; Xu, Yongjin; Knapp, Mark S.; Elling, Robert; Burger, Matthew T.; Ni, Zhi-Jie; Smith, Aaron; Lan, Jiong; Williams, Teresa E.; Verhagen, Joelle; Huh, Kay; Merritt, Hanne; Chan, John; Kaufman, Susan; Voliva, Charles F.; Pecchi, Sabina

2016-02-01

Alterations in PI3K/AKT signaling are known to be implicated with tumorigenesis. The PI3 kinases family of lipid kinases has been an attractive therapeutic target for cancer treatment. Imidazopyridine compound 1, a potent, selective, and orally available pan-PI3K inhibitor, identified by scaffold morphing of a benzothiazole hit, was further optimized in order to achieve efficacy in a PTEN-deleted A2780 ovarian cancer mouse xenograft model. With a hypothesis that a planar conformation between the core and the 6-heteroaryl ring will allow for the accommodation of larger 5'-substituents in a hydrophobic area under P-loop, SAR efforts focused on 5'-alkoxy heteroaryl rings at the 6-position of imidazopyridine and imidazopyridazine cores that have the same dihedral angle of zero degrees. 6'-Alkoxy 5'-aminopyrazines in the imidazopyridine series were identified as the most potent compounds in the A2780 cell line. Compound 14 with 1,1,1-trifluoroisopropoxy group at 6'-position demonstrated excellent potency and selectivity, good oral exposure in rats and in vivo efficacy in A2780 tumor-bearing mouse. Also, we disclose the X-ray co-crystal structure of one enantiomer of compound 14 in PI3Kα, confirming that the trifluoromethyl group fits nicely in the hydrophobic hot spot under P-loop.

Discovery of imidazo[1,2-a]-pyridine inhibitors of pan-PI3 kinases that are efficacious in a mouse xenograft model.

Science.gov (United States)

Han, Wooseok; Menezes, Daniel L; Xu, Yongjin; Knapp, Mark S; Elling, Robert; Burger, Matthew T; Ni, Zhi-Jie; Smith, Aaron; Lan, Jiong; Williams, Teresa E; Verhagen, Joelle; Huh, Kay; Merritt, Hanne; Chan, John; Kaufman, Susan; Voliva, Charles F; Pecchi, Sabina

2016-02-01

Alterations in PI3K/AKT signaling are known to be implicated with tumorigenesis. The PI3 kinases family of lipid kinases has been an attractive therapeutic target for cancer treatment. Imidazopyridine compound 1, a potent, selective, and orally available pan-PI3K inhibitor, identified by scaffold morphing of a benzothiazole hit, was further optimized in order to achieve efficacy in a PTEN-deleted A2780 ovarian cancer mouse xenograft model. With a hypothesis that a planar conformation between the core and the 6-heteroaryl ring will allow for the accommodation of larger 5'-substituents in a hydrophobic area under P-loop, SAR efforts focused on 5'-alkoxy heteroaryl rings at the 6-position of imidazopyridine and imidazopyridazine cores that have the same dihedral angle of zero degrees. 6'-Alkoxy 5'-aminopyrazines in the imidazopyridine series were identified as the most potent compounds in the A2780 cell line. Compound 14 with 1,1,1-trifluoroisopropoxy group at 6'-position demonstrated excellent potency and selectivity, good oral exposure in rats and in vivo efficacy in A2780 tumor-bearing mouse. Also, we disclose the X-ray co-crystal structure of one enantiomer of compound 14 in PI3Kα, confirming that the trifluoromethyl group fits nicely in the hydrophobic hot spot under P-loop. Copyright © 2016 Elsevier Ltd. All rights reserved.

Discovery of dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer

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Nodin Björn

2012-01-01

Full Text Available Abstract Background The Dachshund homolog 2 (DACH2 gene has been implicated in development of the female genital tract in mouse models and premature ovarian failure syndrome, but to date, its expression in human normal and cancerous tissue remains unexplored. Using the Human Protein Atlas as a tool for cancer biomarker discovery, DACH2 protein was found to be differentially expressed in epithelial ovarian cancer (EOC. Here, the expression and prognostic significance of DACH2 was further evaluated in ovarian cancer cell lines and human EOC samples. Methods Immunohistochemical expression of DACH2 was examined in tissue microarrays with 143 incident EOC cases from two prospective, population-based cohorts, including a subset of benign-appearing fallopian tubes (n = 32. A nuclear score (NS, i.e. multiplier of staining fraction and intensity, was calculated. For survival analyses, cases were dichotomized into low (NS 3 using classification and regression tree analysis. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the impact of DACH2 expression on survival. DACH2 expression was analysed in the cisplatin sensitive ovarian cancer cell line A2780 and its cisplatin resistant derivative A2780-Cp70. The specificity of the DACH2 antibody was tested using siRNA-mediated silencing of DACH2 in A2780-Cp70 cells. Results DACH2 expression was considerably higher in the cisplatin resistant A2780-Cp70 cells compared to the cisplatin-sensitive A2780 cells. While present in all sampled fallopian tubes, DACH2 expression ranged from negative to strong in EOC. In EOC, DACH2 expression correlated with several proteins involved in DNA integrity and repair, and proliferation. DACH2 expression was significantly higher in carcinoma of the serous subtype compared to non-serous carcinoma. In the full cohort, high DACH2 expression was significantly associated with poor prognosis in univariable analysis, and in carcinoma of the serous subtype

BRCA1 Expression is an Important Biomarker for Chemosensitivity: Suppression of BRCA1 Increases the Apoptosis via Up-regulation of p53 and p21 During Cisplatin Treatment in Ovarian Cancer Cells

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Ikuo Konishi

2006-01-01

Full Text Available BRCA1 is a tumor suppressor which plays a crucial role in the repair of DNA double-strand breaks, and its abnormality is responsible for hereditary ovarian cancer syndrome. It has recently been reported that reduced expression of BRCA1 is also common in sporadic ovarian carcinoma via its promoter hypermethylation, and that ovarian carcinoma patients negative for BRCA1 expression showed favorable prognosis. To address if BRCA1 expression plays a role in the chemotherapeutic response, we analyzed the effect of BRCA1 suppression on the sensitivity to cisplatin and paclitaxel in ovarian cancer cells. Specific siRNA for BRCA1 gene was transfected into 3 ovarian cancer cell lines with various p53 status. Reduced expression of BRCA1 by transfection of BRCA1-siRNA resulted in a 5.3-fold increase in sensitivity to cisplatin in p53-wild A2780 cells, but not in p53-mutated A2780/CDDP and p53-deleted SKOV3 cells. Regarding the sensitivity to paclitaxel, BRCA1 suppression caused no significant changes in all the 3 cell lines. For ionizing radiation sensitivity, BRCA1 suppression also showed a significant higher sensitivity in A2780 cells. Growth curve and cell cycle analyses showed no signifi cant differences between BRCA1-siRNA-transfected A2780 cells and control cells. However, cisplatin treatment under suppression of BRCA1 showed a significantly increased apoptosis along with up-regulation of p53 and p21 in A2780 cells. Accordingly, reduced expression of BRCA1 enhances the cisplatin sensitivity and apoptosis via up-regulation of p53 and p21, but does not affect the paclitaxel sensitivity. Expression of BRCA1 might be an important biomarker for cisplatin resistance in ovarian carcinoma.

Exosomes as mediators of platinum resistance in ovarian cancer.

Science.gov (United States)

Crow, Jennifer; Atay, Safinur; Banskota, Samagya; Artale, Brittany; Schmitt, Sarah; Godwin, Andrew K

2017-02-14

Exosomes have been implicated in the cell-cell transfer of oncogenic proteins and genetic material. We speculated this may be one mechanism by which an intrinsically platinum-resistant population of epithelial ovarian cancer (EOC) cells imparts its influence on surrounding tumor cells. To explore this possibility we utilized a platinum-sensitive cell line, A2780 and exosomes derived from its resistant subclones, and an unselected, platinum-resistant EOC line, OVCAR10. A2780 cells demonstrate a ~2-fold increase in viability upon treatment with carboplatin when pre-exposed to exosomes from platinum-resistant cells as compared to controls. This coincided with increased epithelial to mesenchymal transition (EMT). DNA sequencing of EOC cell lines revealed previously unreported somatic mutations in the Mothers Against Decapentaplegic Homolog 4 (SMAD4) within platinum-resistant cells. A2780 cells engineered to exogenously express these SMAD4 mutations demonstrate up-regulation of EMT markers following carboplatin treatment, are more resistant to carboplatin, and release exosomes which impart a ~1.7-fold increase in resistance in naive A2780 recipient cells as compared to controls. These studies provide the first evidence that acquired SMAD4 mutations enhance the chemo-resistance profile of EOC and present a novel mechanism in which exchange of tumor-derived exosomes perpetuates an EMT phenotype, leading to the development of subpopulations of platinum-refractory cells.

Near East/South Asia Report, No. 2780.

Science.gov (United States)

1983-07-08

special occasions, festivals and holidays. The Majority and Cheap Meat Several meters from the Governorate of Giza , at a government-run consumer store...are distributed in a single shipment. Muhammad ’Abd-al-Hakim, the owner of a farm near the pyramids said, "Fodder allotments are sufficient for all

Two new ortho benzoquinones from Uncaria rhynchophylla.

Science.gov (United States)

Zhang, Qian; Chen, Lei; Hu, Le-Jian; Liu, Wen-Yuan; Feng, Feng; Qu, Wei

2016-03-01

The present study was designed to determine the chemical constituents of the stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated and purified from CH2Cl2 fraction by chromatography. Their structures were elucidated by spectroscopic analyses. Their cytotoxicity was tested using MTT method. Two new ortho benzoquinones, 3-diethylamino-5-methoxy-1, 2-benzoquinone (1) and 3-ethylamino-5-methoxy-1, 2-benzoquinone (2), together with a known compound isorhynchophyllic acid (3) were isolated from U. rhynchophylla. These compounds were evaluated for their cytotoxicity against cancer cells A549, HepG2 and A2780. Compounds 1 and 2 were new ortho benzoquinones and showed weak antiproliferative activities on A549, HepG2 and A2780 cells. Compound 3 significantly inhibited the proliferation of A549, HepG2 and A2780 cells with IC50 values being 5.8, 12.8 and 11.8 µmol·L(-1), respectively. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Synthesis, crystal structure and anticancer activity of tetrakis(N-isopropylimidazolidine-2-selenone)platinum(II) chloride

Science.gov (United States)

Ahmad, Saeed; Altoum, Ali Osman S.; Vančo, Ján; Křikavová, Radka; Trávníček, Zdeněk; Dvořák, Zdeněk; Altaf, Muhammad; Sohail, Manzar; Isab, Anvarhusein A.

2018-01-01

A Platinum(II) complex of N-isopropylimidazolidine-2-selenone (i-PrImSe), [Pt(i-PrImSe)4]Cl2 (1) was prepared and characterized by elemental analysis, IR and NMR (1H, 13C, 77Se &195Pt) spectroscopy, and X-ray crystallography. The structure of 1 consists of [Pt(i-PrImSe)4]2+ complex ion and chloride counter ions. The platinum(II) atom adopts a distorted square planar geometry. The in vitro antitumor activity of 1 as well as cisplatin, was evaluated by MTT assay against human; ovarian carcinoma A2780 and its cisplatin-resistant subline A2780R, prostate cancer 22Rv1 and breast cancer MCF-7 cell lines. The title complex displayed the activity against the A2780 cells (IC50 = 30.8 μM) at the level comparable to cisplatin (IC50 = 26.8 μM). The interaction studies with sulfur-containing biomolecules revealed its ability to form a variety of intermediates and oxidized species with L-cysteine and reduced glutathione.

Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology

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Sanad Alonezi

2016-10-01

Full Text Available In the present study, liquid chromatography-mass spectrometry (LC-MS was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive and A2780CR (cisplatin-resistant in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists. Principal component analysis (PCA gave clear separation between the cisplatin-sensitive and resistant strains and their respective controls. The cisplatin-resistant cells were slightly more sensitive to melittin than the sensitive cells with IC50 values of 4.5 and 6.8 μg/mL respectively, although the latter cell line exhibited the greatest metabolic perturbation upon treatment. The changes induced by melittin in the cisplatin-sensitive cells led mostly to reduced levels of amino acids in the proline/glutamine/arginine pathway, as well as to decreased levels of carnitines, polyamines, adenosine triphosphate (ATP and nicotinamide adenine dinucleotide (NAD+. The effects on energy metabolism were supported by the data from the Biolog assays. The lipid compositions of the two cell lines were quite different with the A2780 cells having higher levels of several ether lipids than the A2780CR cells. Melittin also had some effect on the lipid composition of the cells. Overall, this study suggests that melittin might have some potential as an adjuvant therapy in cancer treatment.

Connectivity dynamics since the Last Glacial Maximum in the northern Andes: a pollen-driven framework to assess potential migration

NARCIS (Netherlands)

Flantua, S.G.A.; Hooghiemstra, H.; van Boxel, J.H.; Cabrera, M.; González-Carranza, Z.; González-Arango, C.; Stevens, W.D.; Montiel, O.M.; Raven, P.H.

2014-01-01

We provide an innovative pollen-driven connectivity framework of the dynamic altitudinal distribution of North Andean biomes since the Last Glacial Maximum (LGM). Altitudinally changing biome distributions reconstructed from a pollen record from Lake La Cocha (2780 m) are assessed in terms of their

Modelirovanije zemnoj kory Ukrajiny po rezultatam magnitotelluričeskich issledovanij s ispolzovanijem novych metodik inversij

Czech Academy of Sciences Publication Activity Database

Kováčiková, Světlana; Logvinov, I. M.; Pek, Josef; Tarasov, V. N.

2016-01-01

Roč. 38, č. 6 (2016), s. 83-100 ISSN 0203-3100 Institutional support: RVO:67985530 Keywords : conductivity structure * Earth’s crust * Ukrainian Carpathians * Kirovograd anomaly of conductivity * Voronezh massif decline Subject RIV: DE - Earth Magnetism, Geodesy, Geography OBOR OECD: Physical geography

Selenium in bread and durum wheats grown under a soil-supplementation regime in actual field conditions, determined by cyclic and radiochemical neutron activation analysis

Czech Academy of Sciences Publication Activity Database

Galinha, C.; Pacheco, A. M. G.; Freitas, M. C.; Fikrle, Marek; Kučera, Jan; Coutinho, J.; Macas, B.; Almeida, A. S.; Wolterbeek, H. T.

2014-01-01

Roč. 2014, AUG (2014), s. 3499 ISSN 1588-2780 R&D Projects: GA MŠk(XE) LM2011019 Institutional support: RVO:61389005 Keywords : agronomy * biofortification * Selenium * supplementation * wheat * NAA Subject RIV: GM - Food Processing

Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

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Shailendra Giri

Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

Science.gov (United States)

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-02-24

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

CSIR ScienceScope: Art and science of modelling and simulation

CSIR Research Space (South Africa)

CSIR

2008-03-01

Full Text Available -2780 I CSRR Ma)ewialx Science and Manufac)uwing Pretoria 012 841-4392 Johannesburg 011 482-1300 Port olizabeth 041 508-3200 Cape Town 021 685-4329 I CSRR Na)uwal Rexouwcex and )he En0iwonmen) Pretoria 012 841-4005 Johannesburg 011 358...) En0iwonmen) Pretoria 012 841-3871 Stellenbosch 021 888-2508 I CSRR Defencec Neacec Safe)y and Secuwi)y Pretoria 012 841-2780 I CSRR Ma)ewialx Science and Manufac)uwing Pretoria 012 841-4392 Johannesburg 011 482-1300 Port olizabeth 041 508...

4-Hydroxy estradiol but not 2-hydroxy estradiol induces expression of hypoxia-inducible factor 1α and vascular endothelial growth factor A through phosphatidylinositol 3-kinase/Akt/FRAP pathway in OVCAR-3 and A2780-CP70 human ovarian carcinoma cells

International Nuclear Information System (INIS)

Gao Ning; Nester, Rebecca A.; Sarkar, Mohamadi A.

2004-01-01

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of HIF-1α and HIF-1β subunits. HIF-1 expression is induced by hypoxia, growth factors, and activation of oncogenes. HIF-1 activates downstream target genes such as vascular endothelial growth factor A (VEGF-A), which plays an important role in tumor progression and angiogenesis. Estrogen exposure is considered to be the major risk factor for ovarian cancer. Estradiol (E2) is usually metabolized by CYP1A1/1A2 and CYP3A4 to the 2-hydroxy estradiol (2-OHE2) and 4-hydroxy estradiol (4-OHE2) in human liver. Many reports have suggested that the formation of 4-OHE2 is important for mammary carcinogenesis. However, the formation of 2-OHE2 may play an important role in exhibiting anticarcinogenic effects. In the present study, we have demonstrated that one of the catechol estrogen metabolites of E2, 4-OHE2, induces HIF-1α and VEGF-A expression at protein level in two human ovarian cancer cell lines, OVCAR-3 and A2780-CP70 cells, in dose- and time-dependent manners, whereas the other catechol estrogen metabolite of E2, 2-OHE2, does not alter HIF-1α and VEGF-A expression. To explore the mechanism of 4-OHE2-induced HIF-1α and VEGF-A expression, we studied whether phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase (MAPK) signaling pathways are involved in 4-OHE2-induced HIF-1α and VEGF-A expression. Our findings indicate that PI3K inhibitors, LY294002 and wortmannin, inhibited HIF-1α and VEGF-A expression, whereas MAPK inhibitor, PD98059, did not alter HIF-1α and VEGF-A expression induced by 4-OHE2. 4-OHE2, but not 2-OHE2, also induced Akt phosphorylation at Ser473 in dose- and time-dependent manners, and LY294002 and wortmannin inhibited Akt phosphorylation at Ser473 induced by 4-OHE2. Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1α and VEGF-A expression. These results suggest that the PI3K

Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening

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John J. O'Leary

2013-01-01

Full Text Available Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9 as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant and A2780 (cisplatin-sensitive ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

International Nuclear Information System (INIS)

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-01-01

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues

Determination of elemental impurities in phosphoric acid by INAA employing a novel method of phosphate precipitation

Czech Academy of Sciences Publication Activity Database

Kameník, Jan; Amsil, H.; Kučera, Jan

2014-01-01

Roč. 2014, AUG (2014), s. 3455 ISSN 1588-2780 R&D Projects: GA ČR(CZ) GBP108/12/G108; GA MŠk(XE) LM2011019 Institutional support: RVO:61389005 Keywords : instrumental neutron activation analysis * phosphoric acid * elemental impurities * isothermal distillation Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

Synthesis, Characterization and in Vitro Antitumor Activity of Platinum(II Oxalato Complexes Involving 7-Azaindole Derivatives as Coligands

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Pavel Štarha

2014-07-01

Full Text Available The platinum(II oxalato complexes [Pt(ox(naza2] (1–3 were synthesized and characterized by elemental analysis (C, H, N, multinuclear NMR spectroscopy (1H, 13C, 15N, 195Pt and electrospray ionization mass spectrometry (ESI-MS; naza = 4-chloro-7-azaindole (4Claza; 1, 3-bromo-7-azaindole (3Braza; 2 or 4-bromo-7-azaindole (4Braza; 3. The prepared substances were screened for their in vitro antitumor activity on the osteosarcoma (HOS and breast adenocarcinoma (MCF7 human cancer cell lines, where 2 showed moderate antitumor effect (IC50 = 27.5 μM, and 18.3 μM, respectively. The complex 2 was further tested on a panel of six others human cancer cell lines, including the malignant melanoma (G361, cervix carcinoma (HeLa, ovarian carcinoma (A2780, cisplatin-resistant ovarian carcinoma (A2780R, lung carcinoma (A549 and prostate adenocarcinoma (LNCaP. This substance was found to be moderate antitumor effective against G361 (IC50 = 17.3 μM, HeLa (IC50 = 31.8 μM and A2780 (IC50 = 19.2 μM cell lines. The complex 2 was also studied by NMR for its solution stability and by ESI-MS experiments for its ability to interact with biomolecules, such as cysteine, glutathione or guanosine 5'-monophosphate.

Driving p53 Response to Bax Activation Greatly Enhances Sensitivity to Taxol by Inducing Massive Apoptosis

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Paola De Feudis

2000-05-01

Full Text Available The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3 were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells.

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Karl Egan

Full Text Available Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.

TET1 promotes cisplatin-resistance via demethylating the vimentin promoter in ovarian cancer.

Science.gov (United States)

Han, Xi; Zhou, Yuanyuan; You, Yuanyi; Lu, Jiaojiao; Wang, Lijie; Hou, Huilian; Li, Jing; Chen, Wei; Zhao, Le; Li, Xu

2017-04-01

The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells. Ectopic expression of TET1 in A2780 cells promoted cisplatin resistance and decreased cytotoxicity induced by cisplatin, while inhibition of TET1 by siRNA transfection in CP70 cells attenuated cisplatin resistance and enhanced cytotoxicity of cisplatin. Increased TET1 induced re-expression of vimentin through active DNA demethylation, and cause partial epithelial-to-mesenchymal (EMT) in A2780 cells. Contrarily, knocking down of TET1 in CP70 cells reduced vimentin expression and reversed EMT process. Immunohistochemical analysis of TET1 in human ovarian cancer tissues revealed that TET1 existed in nucleus and cytoplasm in ovarian cancer tissues. And the expression of nuclear TET1 was positively correlated with residual tumor and chemotherapeutic response. Thus, TET1 expression causes resistance to cisplatin and one of the targets of TET1 action is vimentin in ovarian cancer. © 2017 International Federation for Cell Biology.

7 CFR 400.202 - Definitions.

Science.gov (United States)

2010-01-01

... the data communications protocol (standard) that is a binary synchronous communications (BSC), International Business Systems (IBM)-defined, byte controlled communications protocol, using control characters... second (bps) transmission of data utilizing 3780 (or 2780) protocol. (c) Contract, the see Agency Sales...

In Vitro Antitumor Active Gold(I Triphenylphosphane Complexes Containing 7-Azaindoles

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Pavel Štarha

2016-12-01

Full Text Available A series of gold(I complexes of the general composition [Au(naza(PPh3] (1–8 was prepared and thoroughly characterized (e.g., electrospray ionization (ESI mass spectrometry and multinuclear nuclear magnetic resonance (NMR spectroscopy. The N1-deprotonated anions of 7-azaindole or its derivatives (naza are coordinated to the metal centre through the N1 atom of their pyrrole ring, as proved by a single crystal X-ray analysis of the complexes [Au(3I5Braza(PPh3] (7 and [Au(2Me4Claza(PPh3]·½H2O (8′. The in vitrocytotoxicity of the complexes 1–8 was studied against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the MRC-5 human normal fibroblast cell line. The complexes 4, 5, and 8, containing deprotonated 3-iodo-7-azaindole, 5-bromo-7-azaindole, and 2-methyl-4-chloro-7-azaindole (2Me4Claza, respectively, showed significantly higher potency (IC50 = 2.8–3.5 µM than cisplatin (IC50 = 20.3 µM against the A2780 cells and markedly lower effect towards the MRC-5 non-cancerous cells (IC50 = 26.0–29.2 µM, as compared with the mentioned A2780 cancer cells. The results of the flow cytometric studies of the A2780 cell cycle perturbations revealed a G2-cell cycle phase arrest of the cells treated by the representative complexes 1 and 5, which is indicative of a different mechanism of action from cisplatin (induced S-cell cycle phase arrest. The stability of the representative complex 8 in the water-containing solution as well as its ability to interact with the reduced glutathione, cysteine and bovine serum albumin was also studied using 1H and 31P-NMR spectroscopy (studied in the 50% DMF-d7/50% D2O mixture and ESI+ mass spectrometry (studied in the 50% DMF/50% H2O mixture; DMF = dimethylformamide. The obtained results are indicative for the release of the N-donor azaindole-based ligand in the presence of the used biomolecules.

MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines

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Kumar Smriti

2011-09-01

Full Text Available Abstract Background Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Methods The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs between cis-platin sensitive (A2780, and cis-platin resistant (A2780/CP70 cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. Results Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. Conclusions Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated

Effect of altered innervation and thyroid hormones on myosin heavy chain expression and fiber type transitions: a mini-review

Czech Academy of Sciences Publication Activity Database

Soukup, Tomáš; Smerdu, V.

2015-01-01

Roč. 143, č. 2 (2015), s. 123-130 ISSN 0948-6143 R&D Projects: GA MŠk(CZ) LH12058; GA MŠk(CZ) 7AMB14SK123 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional support: RVO:67985823 Keywords : muscle fiber types * muscle regeneration * muscle transplantation * MyHC isoforms * thyroid hormone status * innervation Subject RIV: EA - Cell Biology Impact factor: 2.780, year: 2015

Cytotoxicity of Nanoliposomal Cisplatin Coated with Synthesized ...

African Journals Online (AJOL)

Purpose: To evaluate the cytotoxicity of pegylated nanoliposomal cisplatin on human ovarian cancer cell line A2780CP. Methods: Synthesized methoxypolyethylene glycol (mPEG) propionaldehyde was characterized by 1Hnuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy (FTIR) and used ...

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

OpenAIRE

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.; Kingston, David G. I.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 an...

Synthesis, characterisation and biological properties of gold(III) compounds with modified bipyridine and bipyridylamine ligands.

Science.gov (United States)

Casini, Angela; Diawara, Mariam Celine; Scopelliti, Rosario; Zakeeruddin, Shaik Mohammed; Grätzel, Michael; Dyson, Paul J

2010-03-07

Square planar gold(III) complexes that contain functionalised bipyridine ligands of general formula [Au(N--N)Cl(2)][PF(6)] [where N--N = 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine and 4,4'-diamino-2,2'-bipyridine] have been prepared and characterised by NMR spectroscopy and mass spectrometry. Two of the complexes have also been characterised in the solid state by X-ray crystallography. In addition, a gold(iii) compound bearing a dipyridin-2-ylamine ligand was also prepared and characterised. The complexes were found to undergo hydrolysis under pseudo-physiological conditions. Moreover, the complexes showed moderate to good cytotoxicity in vitro towards the A2780 human ovarian carcinoma cell line and the cisplatin resistant variant A2780cisR. Reactivity studies with biomolecules, such as reducing agents, plasmid DNA and a model protein (ubiquitin) were also performed to provide tentative insights into the mode of action of the complexes.

Modeling Dry Deposition of Aerosol Particles on Rough Surfaces

Czech Academy of Sciences Publication Activity Database

Hussein, T.; Smolík, Jiří; Kerminen, V.-M.; Kulmala, M.

2012-01-01

Roč. 46, č. 1 (2012), s. 44-59 ISSN 0278-6826 Institutional research plan: CEZ:AV0Z40720504 Keywords : aerosol particles * dry deposition * transport Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.780, year: 2012

Triphenyltin derivatives of sulfanylcarboxylic esters.

Science.gov (United States)

Casas, José S; Couce, María D; Sánchez, Agustín; Seoane, Rafael; Sordo, José; Perez-Estévez, Antonio; Vázquez-López, Ezequiel

2018-03-01

The reaction of 3-(aryl)-2-sulfanylpropenoic acids [H 2 xspa; x: p=3-phenyl-, f=3-(2-furyl)-, t=3-(2-thienyl)-] with methanol or ethanol gave the corresponding methyl (Hxspme) or ethyl (Hxspee) esters. The reaction of these esters (HL) with triphenyltin(IV) hydroxide gave compounds of the type [SnPh 3 L], which were isolated and characterized as solids by elemental analysis, IR spectroscopy and mass spectrometry and in solution by multinuclear ( 1 H, 13 C and 119 Sn) NMR spectroscopy. The structures of [SnPh 3 (pspme)], [SnPh 3 (fspme)] and [SnPh 3 (fspee)] were determined by X-ray diffractometry and the antimicrobial activity against E. coli, S. aureus, B. subtilis, P. aeruginosa, Resistant P. aeruginosa (a strain resistant to 'carbapenem'), and C. albicans was tested and the in vitro cytotoxic activity against the HeLa-229, A2780 and A2780cis cell lines was determined for all compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Organometallic rhodium(III) and iridium(III) cyclopentadienyl complexes with curcumin and bisdemethoxycurcumin co-ligands.

Science.gov (United States)

Pettinari, Riccardo; Marchetti, Fabio; Pettinari, Claudio; Condello, Francesca; Petrini, Agnese; Scopelliti, Rosario; Riedel, Tina; Dyson, Paul J

2015-12-21

A series of half-sandwich cyclopentadienyl rhodium(III) and iridium(III) complexes of the type [Cp*M(curc/bdcurc)Cl] and [Cp*M(curc/bdcurc)(PTA)][SO3CF3], in which Cp* = pentamethylcyclopentadienyl, curcH = curcumin and bdcurcH = bisdemethoxycurcumin as O^O-chelating ligands, and PTA = 1,3,5-triaza-7-phosphaadamantane, is described. The X-ray crystal structures of three of the complexes, i.e. [Cp*Rh(curc)(PTA)][SO3CF3] (5), [Cp*Rh(bdcurc)(PTA)][SO3CF3] (6) and [Cp*Ir(bdcurc)(PTA)][SO3CF3] (8), confirm the expected "piano-stool" geometry. With the exception of 5, the complexes are stable under pseudo-physiological conditions and are moderately cytotoxic to human ovarian carcinoma (A2780 and A2780cisR) cells and also to non-tumorigenic human embryonic kidney (HEK293) cells, but lack the cancer cell selectivity observed for related arene ruthenium(II) complexes.

Ananthakrishna, Prof. Garani

Indian Academy of Sciences (India)

Date of birth: 11 December 1942. Specialization: Theoretical Materials Science, Condensed Matter and Dynamical Systems & Chaos Address: Materials Research Centre, Indian Institute of Science, Bengaluru 560 012, Karnataka Contact: Office: (080) 2293 2780. Residence: (080) 4953 5791. Mobile: 99002 68902

Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model.

Science.gov (United States)

Di Liddo, Rosa; Valente, Sergio; Taurone, Samanta; Zwergel, Clemens; Marrocco, Biagina; Turchetta, Rosaria; Conconi, Maria Teresa; Scarpa, Carlotta; Bertalot, Thomas; Schrenk, Sandra; Mai, Antonello; Artico, Marco

2016-01-20

Among epigenetic enzymes, histone deacetylases (HDACs) are responsible for regulating the expression of an extensive array of genes by reversible deacetylation of nuclear histones as well as a large number of non-histone proteins. Initially proposed for cancer therapy, recently the interest for HDAC inhibitors (HDACi) as orally active, safe, and anti-inflammatory agents is rising due to their ability in reducing the severity of inflammatory and autoimmune diseases. In particular, selective HDAC3, HDAC6, and HDAC8 inhibitors have been described to downregulate the expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Herein, using KB31, C2C12, and 3T3-J2 cell lines, we demonstrated that, under lipopolysaccharide-induced in vitro inflammation, HDAC3/6/8 inhibitor MC2625 and HDAC6-selective inhibitor MC2780 were effective at a concentration of 30 ng/mL to downregulate mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) and to promote the transcription of IL-10 gene, without affecting the cell viability. Afterwards, we investigated by immunohistochemistry the activity of MC2625 and MC2780 at a concentration of 60 ng/kg animal weight to regulate silicone-triggered immune response in C57BL/6J female mice. Our findings evidenced the ability of such inhibitors to reduce host inflammation in silicone implants promoting a thickness reduction of peri-implant fibrous capsule, upregulating IL-10 expression, and reducing the production of both IL-1β and IL-6. These results underline the potential application of MC2625 and MC2780 in inflammation-related diseases.

Cytotoxic and Pro-Apoptotic Effects of Honey Bee Venom and Chrysin on Human Ovarian Cancer Cells

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Elaheh Amini

2015-06-01

Full Text Available Background: The anti-cancer effects of honey bee venom (BV and chrysin might open a new window for treatment of chemo-resistant cancers. This study was designed to evaluate cytotoxic and pro-apoptotic effects of BV and chrysin on A2780cp cistplatin- resistant human ovarian cancer cells. Methods: As per the study objectives, A2780cp cells were categorized to 4 groups: 3 experiment groups (treated either with BV or chrysin or BV + chrysin and 1 control group (untreated cells.  Experiment group cells were cultured and treated by different concentrations of BV and chrysin for 24 hours. Then, experiment and control cells were studied with MTT assay, Annexin V-FITC, DAPI and Acridine Orange / Propidium Iodide statining, flow cytometry, caspase-3 and -9 assay, measurement of intracellular level of reactive oxygen species (ROS and RT-PCR. Results: MTT assay showed that 8 μg/mL BV, 40 µg/ml chrysin and 6 + 15 μg/mL BV + chrysin co-treatment induced 50% cell death on A2780cp cells compared with controls (P < 0.001. Morphological observations by inverted and fluorescent microscopy revealed ROS generation and apoptotic cell death under exposure to BV or chrysin or BV + chrysin co-treatment. Caspase-3 and -9 assay demonstrated that BV and chrysin triggered apoptosis through intrinsic pathway and RT-PCR demonstrated down-regulation of Bcl-2. Conclusion: Honey bee venom and chrysin are effective for destroying chemoresistant ovarian cancer cells through activation of intrinsic apoptosis, which propose them as potential candidates to be used in development of improved chemotherapeutic agents in the future.

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

Science.gov (United States)

Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

2017-03-01

Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

Spurious Additional Warming Reconstructed From Borehole\

Czech Academy of Sciences Publication Activity Database

Šafanda, Jan

2018-01-01

Roč. 45, č. 6 (2018), s. 2780-2785 ISSN 0094-8276 R&D Projects: GA MŠk(CZ) EF16_013/0001792 Institutional support: RVO:67985530 Subject RIV: DC - Siesmology, Volcanology, Earth Structure OBOR OECD: Volcanology Impact factor: 4.253, year: 2016

75 FR 61747 - Union Leader Corporation; Supplemental Notice That Initial Market-Based Rate Filing Includes...

Science.gov (United States)

2010-10-06

... of Union Leader Corporation's application for market-based rate authority, with an accompanying rate... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER10-2780-000] Union Leader Corporation; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket Section...

Unbounded planar domains whose second nodal line does not touch the boundary

Czech Academy of Sciences Publication Activity Database

Freitas, P.; Krejčiřík, David

2007-01-01

Roč. 14, č. 1 (2007), s. 107-111 ISSN 1073-2780 R&D Projects: GA MŠk LC06002 Institutional research plan: CEZ:AV0Z10480505 Keywords : Dirichlet Laplacian * eigenfunctions * nodal line Subject RIV: BA - General Mathematics Impact factor: 0.702, year: 2007

Inhibitory specificity and insecticidal selectivity of alpha-amylase inhibitor from Phaseolus vulgaris

Czech Academy of Sciences Publication Activity Database

Kluh, Ivan; Horn, Martin; Hýblová, Jana; Hubert, J.; Dolečková, Lucie; Voburka, Zdeněk; Kudlíková, I.; Kocourek, F.; Mareš, Michael

2005-01-01

Roč. 66, - (2005), 31-39 ISSN 0031-9422 R&D Projects: GA MŠk(CZ) OC D16.001 Institutional research plan: CEZ:AV0Z4055905 Keywords : enzyme inhibition * digestive enzyme Subject RIV: FD - Oncology ; Hematology Impact factor: 2.780, year: 2005

Ovarian and Breast Cancer Spheres Are Similar in Transcriptomic Features and Sensitive to Fenretinide

Directory of Open Access Journals (Sweden)

Haiwei Wang

2013-01-01

Full Text Available Cancer stem cells (CSCs are resistant to chemotherapy and are ability to regenerate cancer cell populations, thus attracting much attention in cancer research. In this report, we first demonstrated that sphere cells from ovarian cancer cell line A2780 shared many features of CSCs, such as resistance to cisplatin and able to initiate tumors in an efficient manner. Then, we conducted cDNA microarray analysis on spheres from ovarian A2780 cells, and from breast MCF7 and SUM159 cells, and found that molecular pathways underlying spheres from these cancer cell lines were similar to a large extent, suggesting that similar mechanisms are involved in the genesis of CSCs in both ovarian and breast cancer types. In addition, we showed that spheres from these cancer types were highly sensitive to fenretinide, a stimulus of oxidative stress-mediated apoptosis in cancer cells. Thus, our results not only provide important insights into mechanisms underlying CSCs in ovarian and breast cancer, but also lead to the development of more sophisticated protocols of cancer therapy in near future.

22 CFR 127.10 - Civil penalty.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Civil penalty. 127.10 Section 127.10 Foreign... Civil penalty. (a) The Assistant Secretary of State for Political-Military Affairs is authorized to impose a civil penalty in an amount not to exceed that authorized by 22 U.S.C. 2778, 2779a and 2780 for...

Determination of 129 I in biomonitors collected in the vicinity of a nuclear power plant by neutron activation analysis

Czech Academy of Sciences Publication Activity Database

Krausová, Ivana; Kučera, Jan; Světlík, Ivo

2012-01-01

Roč. 293, 13Sep2012 (2012), s. 1-6 ISSN 1588-2780 R&D Projects: GA ČR(CZ) GBP108/12/G108; GA MŠk(XE) LM2011019 Institutional support: RVO:61389005 Keywords : Iodine-129 * neutron activation analysis * biomonitor * nuclear power plant * Thyroid gland Subject RIV: CB - Analytical Chemistry, Separation http://download.springer.com/static/pdf/725/art%253A10.1007%252Fs10967-012-2200-5.pdf?auth66=1361263915_42267d28376ca81c4fc0de53c3cb59f4&ext=.pdf

Experiences in the formalisation and verification of medical protocols

OpenAIRE

Balser, Michael

2003-01-01

Experiences in the formalisation and verification of medical protocols / M. Balser ... - In: Artificial intelligence in medicine : 9th Conference on Artificial Intelligence in Medicine in Europe, AIME 2003, Protaras, Cyprus, October 18 - 22, 2003 ; proceedings / Michel Dojat ... (eds.). - Berlin u.a. : Springer, 2003. - S. 132-141. - (Lecture notes in computer science ; 2780 : Lecture notes in artificial intelligence)

Coloring of radiation damages in ion-implanted poly(aryl ether ether ketone): LiCl uptake and thermal desorption

Czech Academy of Sciences Publication Activity Database

Červená, Jarmila; Vacík, Jiří; Hnatowicz, Vladimír; Švorčík, V.; Kobayashi, Y.

2002-01-01

Roč. 83, - (2002), s. 2780-2784 ISSN 0021-8995 R&D Projects: GA ČR GA203/99/1626; GA AV ČR IAA7011908; GA AV ČR KSK1010104 Keywords : irradiated peek Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 0.927, year: 2002

Interactions of hydrated divalent metal cations with nucleic acid bases. How to relate the gas phase data to solution situation and binding selectivity in nucleic acids

Czech Academy of Sciences Publication Activity Database

Šponer, Judit E.; Sychrovský, Vladimír; Hobza, Pavel; Šponer, Jiří

2004-01-01

Roč. 6, č. 10 (2004), s. 2772-2780 ISSN 1463-9076 R&D Projects: GA MŠk LN00A016; GA MŠk LN00A032 Grant - others:Wellcome Trust(GB) GR067507MF Institutional research plan: CEZ:AV0Z5004920 Keywords : nucleic acids * gas phase * guanine Subject RIV: BO - Biophysics Impact factor: 2.076, year: 2004

Cancer-associated fibroblasts are not formed from cancer cells by epithelial-to-mesenchymal transition in nu/nu mice

Czech Academy of Sciences Publication Activity Database

Dvořánková, B.; Smetana Jr, K.; Říhová, Blanka; Kučera, J.; Mateu, R.; Szabo, P.

2015-01-01

Roč. 143, č. 5 (2015), s. 463-469 ISSN 0948-6143 R&D Projects: GA ČR(CZ) GAP301/12/1254; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Cancer stroma * Cancer-associated fibroblast * Myofibroblast Subject RIV: EC - Immunology Impact factor: 2.780, year: 2015

Bonding Strength of Universal Adhesives To Er,Cr:YSGG Laser ...

African Journals Online (AJOL)

2018-02-07

Feb 7, 2018 ... E-mail: kerimayar@biruni.edu.tr smear layer ... increased, owing to their greater aesthetic properties and the potential ... produced by the selective ablation of the intertubular dentin ... 2.780 nm, power of 1.5 W, frequency of 20 Hz, pulse duration ..... Lopes RM, Trevelin LT, da Cunha SRB, de Oliveira RF, de.

Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells

Science.gov (United States)

2012-01-01

Introduction The taxanes paclitaxel and docetaxel are widely used in the treatment of breast, ovarian, and other cancers. Although their cytotoxicity has been attributed to cell-cycle arrest through stabilization of microtubules, the mechanisms by which tumor cells die remains unclear. Paclitaxel has been shown to induce soluble tumor necrosis factor alpha (sTNF-α) production in macrophages, but the involvement of TNF production in taxane cytotoxicity or resistance in tumor cells has not been established. Our study aimed to correlate alterations in the TNF pathway with taxane cytotoxicity and the acquisition of taxane resistance. Methods MCF-7 cells or isogenic drug-resistant variants (developed by selection for surviving cells in increasing concentrations of paclitaxel or docetaxel) were assessed for sTNF-α production in the absence or presence of taxanes by enzyme-linked immunosorbent assay (ELISA) and for sensitivity to docetaxel or sTNF-α by using a clonogenic assay (in the absence or presence of TNFR1 or TNFR2 neutralizing antibodies). Nuclear factor (NF)-κB activity was also measured with ELISA, whereas gene-expression changes associated with docetaxel resistance in MCF-7 and A2780 cells were determined with microarray analysis and quantitative reverse transcription polymerase chain reaction (RTqPCR). Results MCF-7 and A2780 cells increased production of sTNF-α in the presence of taxanes, whereas docetaxel-resistant variants of MCF-7 produced high levels of sTNF-α, although only within a particular drug-concentration threshold (between 3 and 45 nM). Increased production of sTNF-α was NF-κB dependent and correlated with decreased sensitivity to sTNF-α, decreased levels of TNFR1, and increased survival through TNFR2 and NF-κB activation. The NF-κB inhibitor SN-50 reestablished sensitivity to docetaxel in docetaxel-resistant MCF-7 cells. Gene-expression analysis of wild-type and docetaxel-resistant MCF-7, MDA-MB-231, and A2780 cells identified changes

Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

Directory of Open Access Journals (Sweden)

Yun-Jung Choi

2016-12-01

Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

Identifying gaps in the surgical training curriculum in Rwanda through evaluation of operative activity at a teaching hospital.

Science.gov (United States)

Rickard, Jennifer L; Ntakiyiruta, Georges; Chu, Kathryn M

2015-01-01

To define the operations performed by surgical residents at a tertiary referral hospital in Rwanda to help guide development of the residency program. Cross-sectional study of all patients operated by surgical residents from October 2012 to September 2013. University Teaching Hospital of Kigali (Centre Hospitalier Universitaire de Kigali [CHUK]), a public, tertiary referral hospital in Kigali, Rwanda. All patient data were entered into the operative database by surgical residents at CHUK. A total of 2833 cases were entered into the surgical database. Of them, 53 cases were excluded from further analysis because no surgical resident was listed as the primary or assistant surgeon, leaving 2780 cases for analysis. There were 2780 operations involving surgical residents. Of them, 51% of procedures were classified under general surgery, 38% orthopedics, 7% neurosurgery, and 4% urology. Emergency operations accounted for 64% of the procedures, with 56% of those being general surgery and 35% orthopedic. Further, 50% of all operations were trauma, with 71% of those orthopedic and 21% general surgery. Surgical faculty were involved in 45% of operations as either the primary or the assistant surgeons, while the remainder of operations did not involve surgical faculty. Residents were primary surgeons in 68% of procedures and assistant surgeons in 84% of procedures. The operative experience of surgery residents at CHUK primarily involves emergency and trauma procedures. Although this likely reflects the demographics of surgical care within Rwanda, more focus should be placed on elective procedures to ensure that surgical residents are broadly trained. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

40 CFR 60.2780 - What must I include in the deviation report?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false What must I include in the deviation... PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Emissions Guidelines and... the deviation report? In each report required under § 60.2775, for any pollutant or parameter that...

An access to a library of novel triterpene derivatives with a promising pharmacological potential by Ugi and Passerini multicomponent reactions.

Science.gov (United States)

Wiemann, Jana; Heller, Lucie; Csuk, René

2018-04-25

The promising combination of natural product leads and their derivatization by isocyanide-based multicomponent reactions (IMCRs) has gained interest in accessing diversity-oriented libraries with auspicious pharmacological potential. Therefore, a set of 34 Ugi and 3 Passerini products was successfully synthesized starting from naturally occurring triterpenoids, i.e. oleanolic acid (OA) and maslinic acid (MA), followed by a biological evaluation of the novel α-acylamino carboxamides and the α-acyloxy carboxamides in colorimetric SRB assays to determine their cytotoxic potential. Especially, the MA-Ugi products 6a, 6b and 7b showed a remarkable cytotoxicity for A2780 ovarian carcinoma cells in a low μM range. Compounds 6a and 7b induced programmed cell death in part through the apoptosis pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

DKK1 is a potential novel mediator of cisplatin-refractoriness in non-small cell lung cancer cell lines

International Nuclear Information System (INIS)

Salim, Hogir; Zong, Dali; Hååg, Petra; Novak, Metka; Mörk, Birgitta; Lewensohn, Rolf; Lundholm, Lovisa; Viktorsson, Kristina

2015-01-01

Platinum compounds are the mainstay of chemotherapy for lung cancer. Unfortunately treatment failure remains a critical issue since about 60 % of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance. We analyzed global gene expression profiles of NSCLC clones surviving a pulse treatment with cisplatin and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA). Further validation was done using siRNA. The pooled cisplatin-surviving NSCLC clones from each of the biological replicates demonstrated heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (Dickkopf-1, DKK1), DNA repair machinery (XRCC2) and cell-cell/cell-matrix interaction (FMN1, LGALS9) were among the top deregulated genes by microarray in these replicates and were validated by q-RT-PCR. We focused on DKK1 which previously was reported to be overexpressed in NSCLC patients. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones from that biological replicate. Knockdown of DKK1 by siRNA sensitized for cisplatin in two different NSCLC cell lines and in ovarian A2780 cells, but not in the A2780 cis subline made resistant to cisplatin by chronic exposure, suggesting a role of DKK1 in intrinsic but not acquired platinum refractoriness. We identified DKK1 as a possible marker of a cisplatin-refractory phenotype and as a potential novel therapeutic target to improve platinum response of NSCLC cells. The online version of this article (doi:10.1186/s12885-015-1635-9) contains supplementary material, which is available to authorized users

ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling.

Directory of Open Access Journals (Sweden)

Erhong Meng

Full Text Available OBJECTIVE: Aldehyde dehydrogenase (ALDH expressing cells have been characterized as possessing stem cell-like properties. We evaluated ALDH+ ovarian cancer stem cell-like properties and their role in platinum resistance. METHODS: Isogenic ovarian cancer cell lines for platinum sensitivity (A2780 and platinum resistant (A2780/CP70 as well as ascites from ovarian cancer patients were analyzed for ALDH+ by flow cytometry to determine its association to platinum resistance, recurrence and survival. A stable shRNA knockdown model for ALDH1A1 was utilized to determine its effect on cancer stem cell-like properties, cell cycle checkpoints, and DNA repair mediators. RESULTS: ALDH status directly correlated to platinum resistance in primary ovarian cancer samples obtained from ascites. Patients with ALDHHIGH displayed significantly lower progression free survival than the patients with ALDHLOW cells (9 vs. 3 months, respectively p<0.01. ALDH1A1-knockdown significantly attenuated clonogenic potential, PARP-1 protein levels, and reversed inherent platinum resistance. ALDH1A1-knockdown resulted in dramatic decrease of KLF4 and p21 protein levels thereby leading to S and G2 phase accumulation of cells. Increases in S and G2 cells demonstrated increased expression of replication stress associated Fanconi Anemia DNA repair proteins (FANCD2, FANCJ and replication checkpoint (pS317 Chk1 were affected. ALDH1A1-knockdown induced DNA damage, evidenced by robust induction of γ-H2AX and BAX mediated apoptosis, with significant increases in BRCA1 expression, suggesting ALDH1A1-dependent regulation of cell cycle checkpoints and DNA repair networks in ovarian cancer stem-like cells. CONCLUSION: This data suggests that ovarian cancer cells expressing ALDH1A1 may maintain platinum resistance by altered regulation of cell cycle checkpoint and DNA repair network signaling.

In vitro antioxidant activity and phenolic composition of Georgian, Central and West European wines

Czech Academy of Sciences Publication Activity Database

Tauchen, J.; Maršík, Petr; Kvasnicová, Marie; Maghradze, D.; Kokoška, L.; Vaněk, Tomáš; Landa, Přemysl

2015-01-01

Roč. 41, AUG 2015 (2015), s. 113-121 ISSN 0889-1575 R&D Projects: GA MŠk(CZ) LD11005 Grant - others:OP Praha Konkurenceschopnost(XE) CZ.2.16/3.1.00/24014; project CIGA(CZ) 20142012; COST Action(CZ) FA1003 Institutional support: RVO:61389030 Keywords : Red wine * White wine * Antioxidant activity Subject RIV: GM - Food Processing Impact factor: 2.780, year: 2015

miR-30a can inhibit DNA replication by targeting RPA1 thus slowing cancer cell proliferation.

Science.gov (United States)

Zou, Zhenyou; Ni, Mengjie; Zhang, Jing; Chen, Yongfeng; Ma, Hongyu; Qian, Shihan; Tang, Longhua; Tang, Jiamei; Yao, Hailun; Zhao, Chengbin; Lu, Xiongwen; Sun, Hongyang; Qian, Jue; Mao, Xiaoting; Lu, Xulin; Liu, Qun; Zen, Juping; Wu, Hanbing; Bao, Zhaosheng; Lin, Shudan; Sheng, Hongyu; Li, Yunlong; Liang, Yong; Chen, Zhiqiang; Zong, Dan

2016-07-15

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Quantitative Evaluation of Cisplatin Uptake in Sensitive and Resistant Individual Cells by Single-Cell ICP-MS (SC-ICP-MS).

Science.gov (United States)

Corte Rodríguez, M; Álvarez-Fernández García, R; Blanco, E; Bettmer, J; Montes-Bayón, M

2017-11-07

One of the main limitations to the Pt-therapy in cancer is the development of associated drug resistance that can be associated with a significant reduction of the intracellular platinum concentration. Thus, intracellular Pt concentration could be considered as a biomarker of cisplatin resistance. In this work, an alternative method to address intracellular Pt concentration in individual cells is explored to permit the evaluation of different cell models and alternative therapies in a relatively fast way. For this aim, total Pt analysis in single cells has been implemented using a total consumption nebulizer coupled to inductively coupled plasma mass spectrometric detection (ICP-MS). The efficiency of the proposed device has been evaluated in combination with flow cytometry and turned out to be around 25% (cells entering the ICP-MS from the cells in suspension). Quantitative uptake studies of a nontoxic Tb-containing compound by individual cells were conducted and the results compared to those obtained by bulk analysis of the same cells. Both sets of data were statistically comparable. Thus, final application of the developed methodology to the comparative uptake of Pt-species in cisplatin resistant and sensitive cell lines (A2780cis and A2780) was conducted. The results obtained revealed the potential of this analytical strategy to differentiate between different cell lines of different sensitivity to the drug which might be of high medical interest.

Antiproliferative Properties Against Human Breast, Cervical and Ovarian Cancer Cell Lines, and Antioxidant Capacity of Leaf Aqueous Ethanolic Extract from Cotinus coggygria Scop.

Directory of Open Access Journals (Sweden)

Gospodinova Z.

2017-10-01

Full Text Available Cotinus coggygria Scop. leaf aqueous ethanolic extract was examined for its in vitro antiproliferative and antioxidant activity. Antiproliferative effect was assessed on four human gynecological cancer cell lines: breast (MCF7, T47D, cervical (HeLa and ovarian (A2780 and compared to the cell growth inhibitory effect on non-cancerous breast epithelial cell line MCF10A using MTT cell proliferation assay. Radical scavenging assay with DPPH was applied to evaluate antioxidant potential of the extract. The obtained results showed that the herb inhibited cell growth of all of the tested cancer cell lines and the highest was the cytostatic effect on A2780 cells with a half maximal inhibitory concentration (IC50 value of 30.8 μg/ml. For the other cell lines the IC50 values were in the range of 55-122.7 μg/ml. Additionally, the extract exerted considerably weaker reduction in cell proliferation of the non-cancerous cell line MCF10A compared to cancer cells, which indicates for antiproliferative selectivity. C. coggygria extract showed high free radical scavenging activity with an IC50 value of 11.2 μg/ml. The obtained data provide evidence for pharmacological potential of the tested extract and future more detailed studies concerning the molecular mechanisms of the anticancer effect of the herb are needed.

The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

Science.gov (United States)

Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

2015-04-01

Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (pstar extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (pstar methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

The varieties of religious development in adulthood: a longitudinal investigation of religion and rational choice.

Science.gov (United States)

McCullough, Michael E; Enders, Craig K; Brion, Sharon L; Jain, Andrea R

2005-07-01

The authors used growth mixture models to study religious development during adulthood (ages 27-80) in a sample of individuals who were identified during childhood as intellectually gifted. The authors identified 3 discrete trajectories of religious development: (a) 40% of participants belonged to a trajectory class characterized by increases in religiousness until midlife and declines in later adulthood; (b) 41% of participants belonged to a trajectory class characterized by very low religiousness in early adulthood and age-related decline; and (c) 19% of participants belonged to a trajectory class characterized by high religiousness in early adulthood and age-related increases. Gender, strength of religious upbringing, number of children, marrying, and agreeableness predicted membership in the trajectory classes. Results were largely consistent with the rational choice theory of religious involvement.

Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane

Directory of Open Access Journals (Sweden)

Huaping Chen

2013-01-01

Full Text Available Advanced-stage ovarian cancer is characterized by high mortality due to development of resistance to conventional chemotherapy. Novel compounds that can enhance the efficacy of conventional chemotherapy in ovarian cancer may overcome this drug resistance. Consumption of green tea (epigallocatechin gallate, EGCG and cruciferous vegetables (sulforaphane, SFN is inversely associated with occurrence of ovarian cancer and has anticancer effects through targeting multiple molecules in cancer cells. However, the effects of EGCG and SFN combinational treatment on ovarian cancer cells and on efficacy of cisplatin to these cells are unknown. In this study, EGCG or SFN was used to treat both cisplatin-sensitive (A2780 and cisplatin-resistant (A2780/CP20 ovarian cancer cells alone or in combination with cisplatin. We found that EGCG and SFN combinational treatment can reduce cell viability of both ovarian cancer cell lines time- and dose-dependently. Furthermore, EGCG and SFN combinational treatment can enhance cisplatin-induced apoptosis and G2/M phase arrest, thereby enhancing the efficacy of cisplatin on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. EGCG and SFN combinational treatment upregulated p21 expression induced by cisplatin in cisplatin-sensitive ovarian cancer cells, while p27 expression was not regulated by these treatments. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer.

Cellular responses induced by Cu(II quinolinonato complexes in human tumor and hepatic cells

Directory of Open Access Journals (Sweden)

Trávníček Zdeněk

2012-12-01

Full Text Available Abstract Background Inspired by the unprecedented historical success of cisplatin, one of the most important research directions in bioinorganic and medicinal chemistry is dedicated to the development of new anticancer compounds with the potential to surpass it in antitumor activity, while having lower unwanted side-effects. Therefore, a series of copper(II mixed-ligand complexes of the type [Cu(qui(L]Y · xH2O (1–6, where Hqui = 2-phenyl-3-hydroxy-4(1H-quinolinone, Y = NO3 (1, 3, 5 or BF4 (2, 4, 6, and L = 1,10-phenanthroline (phen (1, 2, 5-methyl-1,10-phenanthroline (mphen (3, 4 and bathophenanthroline (bphen (5, 6, was studied for their in vitro cytotoxicity against several human cancer cell lines (A549 lung carcinoma, HeLa cervix epitheloid carcinoma, G361 melanoma cells, A2780 ovarian carcinoma, A2780cis cisplatin-resistant ovarian carcinoma, LNCaP androgen-sensitive prostate adenocarcinoma and THP-1 monocytic leukemia. Results The tested complexes displayed a stronger cytotoxic effect against all the cancer cells as compared to cisplatin. The highest cytotoxicity was found for the complexes 4 (IC50 = 0.36 ± 0.05 μM and 0.56 ± 0.15 μM, 5 (IC50 = 0.66 ± 0.07 μM and 0.73 ± 0.08 μM and 6 (IC50 = 0.57 ± 0.11 μM and 0.70 ± 0.20 μM against A2780, and A2780cis respectively, as compared with the values of 12.0 ± 0.8 μM and 27.0 ± 4.6 μM determined for cisplatin. Moreover, the tested complexes were much less cytotoxic to primary human hepatocytes than to the cancer cells. The complexes 5 and 6 exhibited significantly high ability to modulate secretion of the pro-inflammatory cytokines TNF-α (2873 ± 238 pg/mL and 3284 ± 139 pg/mL for 5, and 6 respectively and IL-1β (1177 ± 128 pg/mL and 1087 ± 101 pg/mL for 5, and 6 respectively tested on the lipopolysaccharide (LPS-stimulated THP-1 cells as compared with the values of 1173�

Reduced graphene oxide–silver nanoparticle nanocomposite: a potential anticancer nanotherapy

Directory of Open Access Journals (Sweden)

Gurunathan S

2015-10-01

Full Text Available Sangiliyandi Gurunathan, Jae Woong Han, Jung Hyun Park, Eunsu Kim, Yun-Jung Choi, Deug-Nam Kwon, Jin-Hoi Kim Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea Background: Graphene and graphene-based nanocomposites are used in various research areas including sensing, energy storage, and catalysis. The mechanical, thermal, electrical, and biological properties render graphene-based nanocomposites of metallic nanoparticles useful for several biomedical applications. Epithelial ovarian carcinoma is the fifth most deadly cancer in women; most tumors initially respond to chemotherapy, but eventually acquire chemoresistance. Consequently, the development of novel molecules for cancer therapy is essential. This study was designed to develop a simple, non-toxic, environmentally friendly method for the synthesis of reduced graphene oxide–silver (rGO–Ag nanoparticle nanocomposites using Tilia amurensis plant extracts as reducing and stabilizing agents. The anticancer properties of rGO–Ag were evaluated in ovarian cancer cells. Methods: The synthesized rGO–Ag nanocomposite was characterized using various analytical techniques. The anticancer properties of the rGO–Ag nanocomposite were evaluated using a series of assays such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, cellular levels of malonaldehyde and glutathione, caspase-3 activity, and DNA fragmentation in ovarian cancer cells (A2780. Results: AgNPs with an average size of 20 nm were uniformly dispersed on graphene sheets. The data obtained from the biochemical assays indicate that the rGO–Ag nanocomposite significantly inhibited cell viability in A2780 ovarian cancer cells and increased lactate dehydrogenase leakage, reactive oxygen species generation, caspase-3 activity, and DNA fragmentation compared with other tested nanomaterials such as graphene oxide, rGO, and AgNPs. Conclusion: T. amurensis plant extract

Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73.

Science.gov (United States)

Lam, Frankie; Abbas, Abdullahi Y; Shao, Hao; Teo, Theodosia; Adams, Julian; Li, Peng; Bradshaw, Tracey D; Fischer, Peter M; Walsby, Elisabeth; Pepper, Chris; Chen, Yi; Ding, Jian; Wang, Shudong

2014-09-15

Dysregulation of cellular transcription and translation is a fundamental hallmark of cancer. As CDK9 and Mnks play pivotal roles in the regulation of RNA transcription and protein synthesis, respectively, they are important targets for drug development. We herein report the cellular mechanism of a novel CDK9 inhibitor CDKI-73 in an ovarian cancer cell line (A2780). We also used shRNA-mediated CDK9 knockdown to investigate the importance of CDK9 in the maintenance of A2780 cells. This study revealed that CDKI-73 rapidly inhibited cellular CDK9 kinase activity and down-regulated the RNAPII phosphorylation. This subsequently caused a decrease in the eIF4E phosphorylation by blocking Mnk1 kinase activity. Consistently, CDK9 shRNA was also found to down-regulate the Mnk1 expression. Both CDKI-73 and CDK9 shRNA decreased anti-apoptotic proteins Mcl-1 and Bcl-2 and induced apoptosis. The study confirmed that CDK9 is required for cell survival and that ovarian cancer may be susceptible to CDK9 inhibition strategy. The data also implied a role of CDK9 in eIF4E-mediated translational control, suggesting that CDK9 may have important implication in the Mnk-eIF4E axis, the key determinants of PI3K/Akt/mTOR- and Ras/Raf/MAPK-mediated tumorigenic activity. As such, CDK9 inhibitor drug candidate CDKI-73 should have a major impact on these pathways in human cancers.

Tumor Vesicle—Associated CD147 Modulates the Angiogenic Capability of Endothelial Cells

Directory of Open Access Journals (Sweden)

Danilo Millimaggi

2007-04-01

Full Text Available Matrix metalloproteinase (MMP degradation of extracellular matrix is thought to play an important role in invasion, angiogenesis, tumor growth, and metastasis. Several studies have demonstrated that CD147/ extracellular MMP inducer, a membrane-spanning molecule highly expressed in tumor cells, may be involved in the progression of malignancies by regulating expression of MMP in peritumoral stromal cells. In the present study we show that CD147 is expressed in microvesicles derived from epithelial ovarian cancer cells and that CD147-positive vesicles may promote an angiogenic phenotype in endothelial cells in vitro. Vesicles shed by human ovarian carcinoma cell lines OVCAR3, SKOV3, and A2780 expressed different levels of CD147 and stimulated proangiogenic activities of human umbilical vein endothelial cells (HUVECs in a CD147-dependent fashion (OVCAR3 > SKOV3 > A2780. Moreover, vesicles shed by ovarian carcinoma cell line CABA I with low CD147 expression had no significant effect on the development of angiogenic phenotype in HUVECs. The treatment of OVCAR3 cells with small interfering RNA against CD147 suppressed the angiogenic potential of OVCAR3-derived microvesicles. However, transfection of CD147 cDNA into the CABA I cell line enabled CABA I-derived vesicles to induce angiogenesis and to promote MMP genes expression in HUVECs. We therefore conclude that vesicles shed by ovarian cancer cells may induce proangiogenic activities of HUVECs by a CD147-mediated mechanism.

Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

Science.gov (United States)

Brandhonneur, N; Hatahet, T; Amela-Cortes, M; Molard, Y; Cordier, S; Dollo, G

2018-04-01

We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of Mo 6 Br 14 cluster unit, (TBA) 2 Mo 6 Br 14 , presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA) 2 Mo 6 Br 14 was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA) 2 Mo 6 Br 14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis and In Vitro Antiproliferative Activity of Novel Androst-5-ene Triazolyl and Tetrazolyl Derivatives

Directory of Open Access Journals (Sweden)

János Wölfling

2011-06-01

Full Text Available A straightforward and reliable method for the regioselective synthesis of steroidal 1,4-disubstituted triazoles and 1,5-disubstituted tetrazoles via copper(I-catalyzed cycloadditions is reported. Heterocycle moieties were efficiently introduced onto the starting azide compound 3β-acetoxy-16β-azidomethylandrost-5-en-17β-ol through use of the “click” chemistry approach. The antiproliferative activities of the newly-synthesized triazoles were determined in vitro on three human gynecological cell lines (HeLa, MCF7 and A2780 using the microculture tetrazolium assay.

A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

DEFF Research Database (Denmark)

Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

2010-01-01

Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitamin...... B(3)). We examined the toxicity profile of APO866 in B6D2F1 mice and the effect of oral administration of nicotinic acid on tissue toxicity. Nicotinic acid (50 mg/kg) protects mice from death and severe toxicity from an APO866 dose (60 mg/kg) four times the monotherapy maximum tolerated dose (15 mg....../kg). In a panel of six cancer cell lines, we find that three (including ML-2 cells) are protected by nicotinic acid in vitro, whereas the cytotoxicity of APO866 remains unaffected in the remaining three (including A2780 cells). A selective biomarker for the protection by nicotinic acid was subsequently identified...

Defect structure of yttria-stabilized zirconia and its influence on the ionic conductivity at elevated temperatures

DEFF Research Database (Denmark)

Goff, J.P.; Hayes, W.; Hull, S.

1999-01-01

The defect structure of cubic fluorite structured yttria-stabilized zirconia (ZrO2)(1-x)(Y2O3)(x) has been investigated over the composition range 0.100(3)less than or equal to x less than or equal to 0.241 (10) and temperatures T(K) up to 2780(10) K, using single-crystal specimens. Analysis of n......, we propose that the anomalous decrease in the ionic conductivity with increasing x is a consequence of the decreasing mobility of the isolated defects, possibly due to blockage by the increasing number of static aggregates....

Isolation of the New Antiplasmodial Butanolide, Malleastrumolide A, from Malleastrum sp. (Meliaceae) from Madagascar.

Science.gov (United States)

Du, Yongle; Abedi, Alexander K; Valenciano, Ana Lisa; Fernández-Murga, Maria L; Cassera, Maria B; Rasamison, Vincent E; Applequist, Wendy L; Miller, James S; Kingston, David G I

2017-12-01

An extract of Malleastrum sp. (Meliaceae) collected in Madagascar by the Madagascar International Cooperative Biodiversity Group was found to have antimalarial activity, with an IC 50 value between 2.5 and 5 μg ml -1 . After purification by liquid-liquid partition, chromatography on a Diaion open column, C 18 SPE and C 18 reversed phase HPLC, the new butanolide, malleastrumolide A, was isolated. The structure of malleastrumolide A was determined by mass spectrometry, NMR, and ECD. The double bond position was determined by cross-metathesis and mass spectrometry. The compound has antiproliferative activity against the A2780 ovarian cancer cell line with an IC 50 value of 17.4 μm and antiplasmodial activity against the drug-resistant Dd2 strain of Plasmodium falciparum with an IC 50 value of 2.74 μm. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

Science.gov (United States)

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC50 values of 0.44 μM (0.14 μg/mL) and 0.045 μg/mL, respectively. A semisynthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. PMID:21480509

D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery

Directory of Open Access Journals (Sweden)

Wu YP

2015-08-01

Full Text Available Yupei Wu,1,* Qian Chu,2,* Songwei Tan,1 Xiangting Zhuang,1 Yuling Bao,1 Tingting Wu,1 Zhiping Zhang1,3,41Tongji School of Pharmacy, 2Department of Oncology, Tongji Hospital, Tongji Medical School, 3Hubei Engineering Research Center for NDDS, 4National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: Paclitaxel (PTX is one of the most effective antineoplastic drugs. Its current clinical administration Taxol® is formulated in Cremophor EL, which causes serious side effects. Nanoparticles (NP with lower systemic toxicity and enhanced therapeutic efficiency may be an alternative formulation of the Cremophor EL-based vehicle for PTX delivery. In this study, novel amphipathic 4-arm-PEG-TPGS derivatives, the conjugation of D-α-tocopherol polyethylene glycol succinate (TPGS and 4-arm-polyethylene glycol (4-arm-PEG with different molecular weights, have been successfully synthesized and used as carriers for the delivery of PTX. These 4-arm-PEG-TPGS derivatives were able to self-assemble to form uniform NP with PTX encapsulation. Among them, 4-arm-PEG5K-TPGS NP exhibited the smallest particle size, highest drug-loading efficiency, negligible hemolysis rate, and high physiologic stability. Therefore, it was chosen for further in vitro and in vivo investigations. Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG5K-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780, non-small cell lung cancer (A549, and breast adenocarcinoma cancer (MCF-7 cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells. More importantly, PTX-loaded 4-arm-PEG5K-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol® in S180 sarcoma-bearing mice models. This study suggested

Synthesis and cytotoxic evaluation of novel C-10 nitrate derivatives of colchicine

International Nuclear Information System (INIS)

Shen, L.H.; Wang, B.; Liu, S.M.

2016-01-01

In our continuing search for more potent anticancer agent, eight novel nitrates couple with C-10 colchicine nitric oxide-releasing derivatives (5a-f and 7a-b) were prepared. These target compounds were assayed for their anti-tumor activity in vitro against four cancer cell lines, including human hepatocellular carcinoma cells (BEL7402), human ovary carcinoma cells (A2780), human lung adenocarcinoma cells (A549) and human breast carcinoma cells (MCF7). Preliminary results indicated that most of them exhibited significant cytotoxic effect toward cancer cells. Compound 7a was investigated further for its more potent cytotoxicity than colchicine. (author)

Biocompatible Lipid Nanoparticles as Carriers To Improve Curcumin Efficacy in Ovarian Cancer Treatment.

Science.gov (United States)

Bondì, Maria Luisa; Emma, Maria Rita; Botto, Chiara; Augello, Giuseppa; Azzolina, Antonina; Di Gaudio, Francesca; Craparo, Emanuela Fabiola; Cavallaro, Gennara; Bachvarov, Dimcho; Cervello, Melchiorre

2017-02-22

Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin released after 24 h from Compritol-Captex, Compritol-Miglyol, and Compritol NLCs being, respectively, equal to 33, 28, and 18% w/w on the total entrapped curcumin. Considering the slower curcumin release profile, Compritol NLCs were chosen to perform successive in vitro studies on ovarian cancer cell lines. The results show that curcumin-loaded NLCs maintain anticancer activity, and reduce cell colony survival more effectively than free curcumin. As an example, the ability of A2780S cells to form colonies was decreased after treatment with 5 μM free curcumin by 50% ± 6, whereas, at the same concentration, the delivery of curcumin with NLC significantly (p < 0.05) inhibited colony formation to approximately 88% ± 1, therefore potentiating the activity of curcumin to inhibit A2780S cell growth. The obtained results clearly suggest that the entrapment of curcumin into NLCs increases curcumin efficacy in vitro, indicating the potential use of NLCs as curcumin delivery systems.

Uso problemático de internet en estudiantes universitarios : factores asociados y diferencias de género

OpenAIRE

Fernández Villa, Tania; Alguacil Ojeda, Juan; Martín, Vicente

2015-01-01

El objetivo del presente trabajo es realizar un análisis descriptivo del uso problemático de Internet en estudiantes universitarios, evaluando la posible asociación con problemas de salud y conductas adictivas, así como diferencias de género en los tipos utilización. Un total de 2780 alumnos participaron en el estudio entre los años 2011 – 2014, siendo un 29% varones (edad 20.8 ± 5.1 años) y un 71% mujeres (edad de 20.3 ± 4.4 años). La prevalencia de uso problemático de Inte...

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer.

Science.gov (United States)

Burger, Matthew T; Pecchi, Sabina; Wagman, Allan; Ni, Zhi-Jie; Knapp, Mark; Hendrickson, Thomas; Atallah, Gordana; Pfister, Keith; Zhang, Yanchen; Bartulis, Sarah; Frazier, Kelly; Ng, Simon; Smith, Aaron; Verhagen, Joelle; Haznedar, Joshua; Huh, Kay; Iwanowicz, Ed; Xin, Xiaohua; Menezes, Daniel; Merritt, Hanne; Lee, Isabelle; Wiesmann, Marion; Kaufman, Susan; Crawford, Kenneth; Chin, Michael; Bussiere, Dirksen; Shoemaker, Kevin; Zaror, Isabel; Maira, Sauveur-Michel; Voliva, Charles F

2011-10-13

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.

Study of LH2 fueled subsonic passenger transport aircraft

Science.gov (United States)

Brewer, G. D.; Morris, R. E.

1976-01-01

The potential of using liquid hydrogen as fuel in subsonic transport aircraft was investigated to explore an expanded matrix of passenger aircraft sizes. Aircraft capable of carrying 130 passengers 2,780 km (1500 n.mi.); 200 passengers 5,560 km (3000 n.mi.); and 400 passengers on a 9,265 km (5000 n.mi.) radius mission, were designed parametrically. Both liquid hydrogen and conventionally fueled versions were generated for each payload/range in order that comparisons could be made. Aircraft in each mission category were compared on the basis of weight, size, cost, energy utilization, and noise.

Maritime Claims Reference Manual.

Science.gov (United States)

1997-01-01

Melenera to Peninsula de Gando From Peninsula de Gando to Moque Arinaga From Moque Arinaga to Punta Tenefe From Punta Tenefe to Playa Maspalomas (E...From Playa Maspalomas (W) to Punta Taozo From Isla de la Aldea to Punta Sardina From Punta Sardina to Punta Ortiz From Punta Ortiz to Punta...to Cabo Ancones 29° 01.10 13° 27.80 From Punta Lima 28° 55.80 13° 36.87 to Punta del Tarjalillo 28° 35.45 13° 49.25 From Punta de la Entallada 28

Biopanning and characterization of peptides with Fe3O4 nanoparticles-binding capability via phage display random peptide library technique.

Science.gov (United States)

You, Fei; Yin, Guangfu; Pu, Ximing; Li, Yucan; Hu, Yang; Huang, Zhongbin; Liao, Xiaoming; Yao, Yadong; Chen, Xianchun

2016-05-01

Functionalization of inorganic nanoparticles (NPs) play an important role in biomedical applications. A proper functionalization of NPs can improve biocompatibility, avoid a loss of bioactivity, and further endow NPs with unique performances. Modification with vairous specific binding biomolecules from random biological libraries has been explored. In this work, two 7-mer peptides with sequences of HYIDFRW and TVNFKLY were selected from a phage display random peptide library by using ferromagnetic NPs as targets, and were verified to display strong binding affinity to Fe3O4 NPs. Fourier transform infrared spectrometry, fluorescence microscopy, thermal analysis and X-ray photoelectron spectroscopy confirmed the presence of peptides on the surface of Fe3O4 NPs. Sequence analyses revealed that the probable binding mechanism between the peptide and Fe3O4 NPs might be driven by Pearson hard acid-hard base specific interaction and hydrogen bonds, accompanied with hydrophilic interactions and non-specific electrostatic attractions. The cell viability assay indicated a good cytocompatibility of peptide-bound Fe3O4 NPs. Furthermore, TVNFKLY peptide and an ovarian tumor cell A2780 specific binding peptide (QQTNWSL) were conjugated to afford a liner 14-mer peptide (QQTNWSLTVNFKLY). The binding and targeting studies showed that 14-mer peptide was able to retain both the strong binding ability to Fe3O4 NPs and the specific binding ability to A2780 cells. The results suggested that the Fe3O4-binding peptides would be of great potential in the functionalization of Fe3O4 NPs for the tumor-targeted drug delivery and magnetic hyperthermia. Copyright © 2016 Elsevier B.V. All rights reserved.

Antiproliferative compounds of Cyphostemma greveana from a Madagascar dry forest.

Science.gov (United States)

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E; Kingston, David G I

2011-04-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxoselina-4,11-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and a new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC(50) values of 0.44 μM (0.14 μg/ml) and 0.045 μg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

A new photoelectric ink based on nanocellulose/CdS quantum dots for screen-printing.

Science.gov (United States)

Tang, Aimin; Liu, Yuan; Wang, Qinwen; Chen, Ruisong; Liu, Wangyu; Fang, Zhiqiang; Wang, Lishi

2016-09-05

CdS quantum dots with excellent photoelectrical properties embedded in nanocellulose could be exploited for use in photoelectrical ink. In this work, nanocellulose/CdS quantum dot composites were fabricated by controlling the carboxylate content of the nanocellulose and the molar ratio of Cd(2+)/-COOH. New photoelectric inks were prepared based on the composites, in which the CdS quantum dots acted as the pigment and the nanocellulose as the binder. The results of the photocurrent of the composites showed that the photocurrent could be tailored by the carboxylate content and the molar ratio of Cd(2+)/-COOH. And the photocurrent could be as high as 2μA. The surface tension of the photoelectric ink was 27.80±0.03mN/m and its viscosity was 30.3mPas. The photoelectric ink was stable with excellent fluidity and rheology, it could therefore be applied to screen-printing and three-dimensional (3D) printing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergistic efficacy in human ovarian cancer cells by histone deacetylase inhibitor TSA and proteasome inhibitor PS-341.

Science.gov (United States)

Fang, Yong; Hu, Yi; Wu, Peng; Wang, Beibei; Tian, Yuan; Xia, Xi; Zhang, Qinghua; Chen, Tong; Jiang, Xuefeng; Ma, Quanfu; Xu, Gang; Wang, Shixuan; Zhou, Jianfeng; Ma, Ding; Meng, Li

2011-05-01

Histone deacetylase inhibitors and proteasome inhibitor are all emerging as new classes of anticancer agents. We chose TSA and PS-341 to identify whether they have a synergistic efficacy on human ovarian cancer cells. After incubated with 500 nM TSA or/and 40 nM PS-341, we found that combined groups resulted in a striking increase of apoptosis and G2/M blocking rates, no matter in A2780, cisplatin-sensitive ovarian cancer cell line OV2008 or its resistant variant C13*. This demonstrated that TSA interacted synergistically with PS-341, which raised the possibility that combined the two drugs may represent a novel strategy in ovarian cancer.

Poster - 14: Batch Effect Reduction in in-vitro Raman Microscopic Radiosensitivity Study Using Ovarian Cancer Cells

International Nuclear Information System (INIS)

Moradi, Hamid; Murugkar, Sangeeta; Ahmad, Abrar; Shepherdson, Dean; Nyiri, Balazs; Vuong, Nhung; Niedbala, Gosia; Vanderhyden, Barbara; Eapen, Libni

2016-01-01

Purpose: To improve classification by reducing batch effect in samples from the ovarian carcinoma cell lines A2780s (parental wild type) and A2780cp (cisplatin cross-radio-resistant), before, right after, and 24 hours after irradiation to 10Gy. Methods: Spectra were acquired with a home built confocal Raman microscope in 3 distinct runs of six samples: unirradiated s&cp (control pair), then 0h and 24h after irradiation. The Raman spectra were noise reduced, then background subtracted with SMIRF algorithm. ∼35 cell spectra were collected from each sample in 1024 channels from 700cm-1 to 1618cm-1. The spectra were analyzed by regularized multiclass LDA. For feature reduction the spectra were grouped into 3 overlapping group pairs: s-cp, 0Gy–10Gy0h and 0Gy10–Gy24h. The three features, the three differences of the mean spectra were mapped to the analysis sub-space by the inverse regularized covariance matrix. The batch effect noticeably confounded the dose and time effect. Results: To remove the batch effect, the 2+2=4D subspace extended by the covariance matrix of the means of the 0Gy control groups was subtracted from the spectra of each sample. Repeating the analysis on the spectra with the control group variability removed, the batch effect was dramatically reduced in the dose and time directions enabling sharp linear discrimination. The cell type classification also improved. Conclusions: We identified a efficient batch effect removal technique crucial to the applicability of Raman microscopy to radiosensitivity studies both on cell cultures and potential clinical diagnostic applications.

Poster - 14: Batch Effect Reduction in in-vitro Raman Microscopic Radiosensitivity Study Using Ovarian Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Moradi, Hamid; Murugkar, Sangeeta; Ahmad, Abrar; Shepherdson, Dean; Nyiri, Balazs; Vuong, Nhung; Niedbala, Gosia; Vanderhyden, Barbara; Eapen, Libni [Carleton University, Carleton University, Carleton University, Carleton University, The Ottawa Hospital Cancer Centre, University of Ottawa, The Ottawa Hospital Cancer Centre, University of Ottawa, The Ottawa Hospital Cancer Centre (Canada)

2016-08-15

Purpose: To improve classification by reducing batch effect in samples from the ovarian carcinoma cell lines A2780s (parental wild type) and A2780cp (cisplatin cross-radio-resistant), before, right after, and 24 hours after irradiation to 10Gy. Methods: Spectra were acquired with a home built confocal Raman microscope in 3 distinct runs of six samples: unirradiated s&cp (control pair), then 0h and 24h after irradiation. The Raman spectra were noise reduced, then background subtracted with SMIRF algorithm. ∼35 cell spectra were collected from each sample in 1024 channels from 700cm-1 to 1618cm-1. The spectra were analyzed by regularized multiclass LDA. For feature reduction the spectra were grouped into 3 overlapping group pairs: s-cp, 0Gy–10Gy0h and 0Gy10–Gy24h. The three features, the three differences of the mean spectra were mapped to the analysis sub-space by the inverse regularized covariance matrix. The batch effect noticeably confounded the dose and time effect. Results: To remove the batch effect, the 2+2=4D subspace extended by the covariance matrix of the means of the 0Gy control groups was subtracted from the spectra of each sample. Repeating the analysis on the spectra with the control group variability removed, the batch effect was dramatically reduced in the dose and time directions enabling sharp linear discrimination. The cell type classification also improved. Conclusions: We identified a efficient batch effect removal technique crucial to the applicability of Raman microscopy to radiosensitivity studies both on cell cultures and potential clinical diagnostic applications.

Problematic Internet Use in University Students: associated factors and differences of gender

OpenAIRE

Fernández-Villa, Tania; Alguacil Ojeda, Juan; Almaraz Gómez, Ana; Cancela Carral, José María; Delgado-Rodríguez, Miguel; García-Martín, Miguel; Jiménez-Mejías, Eladio; Llorca, Javier; Molina, Antonio José; Ortiz-Moncada, Rocío; Valero-Juan, Luiz Félix; Martín, Vicente

2015-01-01

El objetivo del presente trabajo es realizar un análisis descriptivo del uso problemático de Internet en estudiantes universitarios, evaluando la posible asociación con problemas de salud y conductas adictivas, así como diferencias de género en los tipos utilización. Un total de 2780 alumnos participaron en el estudio entre los años 2011 – 2014, siendo un 29% varones (edad 20.8 ± 5.1 años) y un 71% mujeres (edad de 20.3 ± 4.4 años). La prevalencia de uso problemático de Internet evaluada medi...

Meroterpenoids and isoberkedienolactone from endophytic fungus Penicillium sp. associated with Dysosma versipellis.

Science.gov (United States)

Li, Jun-Wei; Duan, Rui-Gang; Zou, Jian-Hua; Chen, Ri-Dao; Chen, Xiao-Guang; Dai, Jun-Gui

2014-06-01

Seven meroterpenoids and five small-molecular precursors were isolated from Penicillium sp., an endophytic fungus from Dysosma versipellis. The structures of new compounds, 11beta-acetoxyisoaustinone (1) and isoberkedienolactone (2) were elucidated based on analysis of the spectral data, and the absolute configuration of 2 was established by TDDFT ECD calculation with satisfactory match to its experimental ECD data. Meroterpenoids originated tetraketide and pentaketide precursors, resepectively, were found to be simultaneously produced in specific fungus of Penicillium species. These compounds showed weak cytotoxicity in vitro against HCT-116, HepG2, BGC-823, NCI-H1650, and A2780 cell lines with IC 50 > 10 micromol x L(-1).

Nuclear COMMD1 Is Associated with Cisplatin Sensitivity in Ovarian Cancer.

Directory of Open Access Journals (Sweden)

Alina Fedoseienko

Full Text Available Copper metabolism MURR1 domain 1 (COMMD1 protein is a multifunctional protein, and its expression has been correlated with patients' survival in different types of cancer. In vitro studies revealed that COMMD1 plays a role in sensitizing cancer cell lines to cisplatin, however, the mechanism and its role in platinum sensitivity in cancer has yet to be established. We evaluated the role of COMMD1 in cisplatin sensitivity in A2780 ovarian cancer cells and the relation between COMMD1 expression and response to platinum-based therapy in advanced stage high-grade serous ovarian cancer (HGSOC patients. We found that elevation of nuclear COMMD1 expression sensitized A2780 ovarian cancer cells to cisplatin-mediated cytotoxicity. This was accompanied by a more effective G2/M checkpoint, and decreased protein expression of the DNA repair gene BRCA1, and the apoptosis inhibitor BCL2. Furthermore, COMMD1 expression was immunohistochemically analyzed in two tissue micro-arrays (TMAs, representing a historical cohort and a randomized clinical trial-based cohort of advanced stage HGSOC tumor specimens. Expression of COMMD1 was observed in all ovarian cancer samples, however, specifically nuclear expression of COMMD1 was only observed in a subset of ovarian cancers. In our historical cohort, nuclear COMMD1 expression was associated with an improved response to chemotherapy (OR = 0.167; P = 0.038, although this association could not be confirmed in the second cohort, likely due to sample size. Taken together, these results suggest that nuclear expression of COMMD1 sensitize ovarian cancer to cisplatin, possibly by modulating the G2/M checkpoint and through controlling expression of genes involved in DNA repair and apoptosis.

Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy.

Science.gov (United States)

Zhao, Jing; Xu, Youwei; Wang, Changyuan; Ding, Yanfang; Chen, Manyu; Wang, Yifei; Peng, Jinyong; Li, Lei; Lv, Li

2017-07-01

Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus ® copolymers entrapping the poorly soluble anticancer drug dioscin. In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus ® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus ® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus ® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein. The average size of the optimized mixed micelle was 67.15 nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration-time curve (AUC) than the free dioscin solution. Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.

Copper(II) Complexes of Phenanthroline and Histidine Containing Ligands: Synthesis, Characterization and Evaluation of their DNA Cleavage and Cytotoxic Activity.

Science.gov (United States)

Leite, Sílvia M G; Lima, Luís M P; Gama, Sofia; Mendes, Filipa; Orio, Maylis; Bento, Isabel; Paulo, António; Delgado, Rita; Iranzo, Olga

2016-11-21

Copper(II) complexes have been intensely investigated in a variety of diseases and pathological conditions due to their therapeutic potential. The development of these complexes requires a good knowledge of metal coordination chemistry and ligand design to control species distribution in solution and tailor the copper(II) centers in the right environment for the desired biological activity. Herein we present the synthesis and characterization of two ligands HL1 and H 2 L2 containing a phenanthroline unit (phen) attached to the amino group of histidine (His). Their copper(II) coordination properties were studied using potentiometry, spectroscopy techniques (UV-vis and EPR), mass spectrometry (ESI-MS) and DFT calculations. The data showed the formation of single copper complexes, [CuL1] + and [CuL2], with high stability within a large pH range (from 3.0 to 9.0 for [CuL1] + and from 4.5 to 10.0 for [CuL2]). In both complexes the Cu 2+ ion is bound to the phen unit, the imidazole ring and the deprotonated amide group, and displays a distorted square pyramidal geometry as confirmed by single crystal X-ray crystallography. Interestingly, despite having similar structures, these copper complexes show different redox potentials, DNA cleavage properties and cytotoxic activity against different cancer cell lines (human ovarian (A2780), its cisplatin-resistant variant (A2780cisR) and human breast (MCF7) cancer cell lines). The [CuL2] complex has lower reduction potential (E pc = -0.722 V vs -0.452 V for [CuL1] + ) but higher biological activity. These results highlight the effect of different pendant functional groups (carboxylate vs amide), placed out of the coordination sphere, in the properties of these copper complexes.

Formation of stable small cell number three-dimensional ovarian cancer spheroids using hanging drop arrays for preclinical drug sensitivity assays.

Science.gov (United States)

Raghavan, Shreya; Ward, Maria R; Rowley, Katelyn R; Wold, Rachel M; Takayama, Shuichi; Buckanovich, Ronald J; Mehta, Geeta

2015-07-01

Ovarian cancer grows and metastasizes from multicellular spheroidal aggregates within the ascites fluid. Multicellular tumor spheroids are therefore physiologically significant 3D in vitro models for ovarian cancer research. Conventional hanging drop cultures require high starting cell numbers, and are tedious for long-term maintenance. In this study, we generate stable, uniform multicellular spheroids using very small number of ovarian cancer cells in a novel 384 well hanging drop array platform. We used novel tumor spheroid platform and two ovarian cancer cell lines (A2780 and OVCAR3) to demonstrate the stable incorporation of as few as 10 cells into a single spheroid. Spheroids had uniform geometry, with projected areas (42.60×10(3)μm-475.22×10(3)μm(2) for A2780 spheroids and 37.24×10(3)μm(2)-281.01×10(3)μm(2) for OVCAR3 spheroids) that varied as a function of the initial cell seeding density. Phalloidin and nuclear stains indicated cells formed tightly packed spheroids with demarcated boundaries and cell-cell interaction within spheroids. Cells within spheroids demonstrated over 85% viability. 3D tumor spheroids demonstrated greater resistance (70-80% viability) to cisplatin chemotherapy compared to 2D cultures (30-50% viability). Ovarian cancer spheroids can be generated from limited cell numbers in high throughput 384 well plates with high viability. Spheroids demonstrate therapeutic resistance relative to cells in traditional 2D culture. Stable incorporation of low cell numbers is advantageous when translating this research to rare patient-derived cells. This system can be used to understand ovarian cancer spheroid biology, as well as carry out preclinical drug sensitivity assays. Copyright © 2015 Elsevier Inc. All rights reserved.

Progress on the biphase turbine at Cerro Prieto

Energy Technology Data Exchange (ETDEWEB)

Cerini, D.; Hays, L.; Studhalter, W. [Douglas Energy Company, Placentia, CA (United States)

1997-12-31

The status of a Biphase turbine power plant being installed at the Cerro Prieto geothermal field is presented. The major modules for the power plant are completed except for a back pressure steam turbine. The power plant will be started in April 1997 with the Biphase turbine alone followed by the addition of the steam turbine module two months later. The current power plant performance level is 2780 kWe due to a decline in the well. An increase in power output to 4060 kWe by adding the flow from another well is planned. The addition of five Biphase power plants with a total power output of 21.2 megawatts is described.

Experimental therapy of ovarian cancer with synthetic makaluvamine analog: in vitro and in vivo anticancer activity and molecular mechanisms of action.

Directory of Open Access Journals (Sweden)

Tao Chen

Full Text Available The present study was designed to determine the biological effects of novel marine alkaloid analog 7-(4-fluorobenzylamino-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H-one (FBA-TPQ on human ovarian cancer cells for its anti-tumor potential and the underlying mechanisms as a novel chemotherapeutic agent. Human ovarian cancer cells (A2780 and OVCAR-3, and Immortalized non-tumorigenic human Ovarian Surface Epithelial cells (IOSE-144, were exposed to FBA-TPQ for initial cytotoxicity evaluation (via MTS assay kit, Promega. The detailed in-vitro (cell level and in-vivo (animal model studies on the antitumor effects and possible underlying mechanisms of action of the compounds were then performed. FBA-TPQ exerted potent cytotoxicity against human ovarian cancer A2780 and OVCAR-3 cells as an effective inhibitor of cell growth and proliferation, while exerting lesser effects on non-tumorigenic IOSE-144 cells. Further study in the more sensitive OVCAR-3 cell line showed that it could potently induce cell apoptosis (Annexin V-FITC assay, G2/M cell cycle arrest (PI staining analysis and also dose-dependently inhibit OVCAR-3 xenograft tumors' growth on female athymic nude mice (BALB/c, nu/nu. Mechanistic studies (both in vitro and in vivo revealed that FBA-TPQ might exert its activity through Reactive Oxygen Species (ROS-associated activation of the death receptor, p53-MDM2, and PI3K-Akt pathways in OVCAR-3 cells, which is in accordance with in vitro microarray (Human genome microarrays, Agilent data analysis (GEO accession number: GSE25317. In conclusion, FBA-TPQ exhibits significant anticancer activity against ovarian cancer cells, with minimal toxicity to non-tumorigenic human IOSE-144 cells, indicating that it may be a potential therapeutic agent for ovarian cancer.

Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

Directory of Open Access Journals (Sweden)

Xie L

2016-11-01

Full Text Available Lisha Xie,1,* Tiancen Zhao,1,2,* Jing Cai,1 You Su,1 Zehua Wang,1 Weihong Dong1 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Obstetrics and Gynecology, Central Hospital of Wuhan, Wuhan, China *These authors contributed equally to this work Objective: The objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX in human choriocarcinoma cells regarding DNA damage response. Methods: Two choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was evaluated by comet assay. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The protein levels of γH2AX, RAD 51 and p53 were analyzed by Western blot. Results: Remarkable DNA strand breaks were observed in MTX-sensitive cell lines (JAR, JEG-3 and MG63 but not in MTX-resistant cancer cells (A2780 and Hela after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of homologous recombination (HR repair gene RAD51 was dramatically suppressed by MTX in a dose- and time-dependent manner, accompanied with the increase in p53. Conclusion: The MTX-induced DNA strand breaks accompanied by deficiencies in HR repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma. Keywords: choriocarcinoma, chemotherapy hypersensitivity, DNA double-strand break, RAD51, p53

Synthesis, Molecular Structure and Cytotoxicity of Molecular Materials Based on Water Soluble Half-Sandwich Rh(III) and Ir(III) Tetranuclear Metalla-Cycles

Science.gov (United States)

Gupta, Gajendra; Murray, Benjamin S.; Dyson, Paul J.; Therrien, Bruno

2013-01-01

The neutral dinuclear complexes [(η5-C5Me5)2Rh2(μ-dhnq)Cl2] (1) and [(η5-C5Me5)2Ir2(μ-dhnq)Cl2] (2) (dhnqH2 = 5,8-dihydroxy-1,4-naphthoquinone) were obtained from the reaction of [(η5-C5Me5)M(μ-Cl)Cl]2 (M = Rh, Ir) with dhnqH2 in the presence of CH3COONa. Treatment of 1 or 2 in methanol with linear ditopic ligands L (L = pyrazine, 4,4′-bipyridine or 1,2-bis(4-pyridyl)ethylene), in the presence of AgCF3SO3, affords the corresponding tetranuclear metalla-rectangles [(η5-C5Me5)4M4(μ-dhnq)2(μ-L)2]4+ (L = pyrazine, M = Rh, 3; M = Ir, 4; L = 4,4′-bipyridine, M = Rh, 5; M = Ir, 6; L = 1,2-bis(4-pyridyl)ethylene, M = Rh, 7; M = Ir, 8). All complexes were isolated as their triflate salts and were fully characterized by infrared, 1H and 13C NMR spectroscopy, and some representative complexes by single-crystal X-ray structure analysis. The X-ray structures of 3, 5 and 6 confirm the formation of the tetranuclear metalla-cycles, and suggest that complexes 5 and 6 possess a cavity of sufficient size to encapsulate small guest molecules. In addition, the antiproliferative activity of the metalla-cycles 3–8 was evaluated against the human ovarian A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) cancer cell lines and on non-tumorigenic human embryonic kidney HEK293 cells. All cationic tetranuclear metalla-rectangles were found to be highly cytotoxic, with IC50 values in the low micromolar range. PMID:28788394

Synthesis, Molecular Structure and Cytotoxicity of Molecular Materials Based on Water Soluble Half-Sandwich Rh(III and Ir(III Tetranuclear Metalla-Cycles

Directory of Open Access Journals (Sweden)

Gajendra Gupta

2013-11-01

Full Text Available The neutral dinuclear complexes [(η5-C5Me52Rh2(μ-dhnqCl2] (1 and [(η5-C5Me52Ir2(μ-dhnqCl2] (2 (dhnqH2 = 5,8-dihydroxy-1,4-naphthoquinone were obtained from the reaction of [(η5-C5Me5M(μ-ClCl]2 (M = Rh, Ir with dhnqH2 in the presence of CH3COONa. Treatment of 1 or 2 in methanol with linear ditopic ligands L (L = pyrazine, 4,4′-bipyridine or 1,2-bis(4-pyridylethylene, in the presence of AgCF3SO3, affords the corresponding tetranuclear metalla-rectangles [(η5-C5Me54M4(μ-dhnq2(μ-L2]4+ (L = pyrazine, M = Rh, 3; M = Ir, 4; L = 4,4′-bipyridine, M = Rh, 5; M = Ir, 6; L = 1,2-bis(4-pyridylethylene, M = Rh, 7; M = Ir, 8. All complexes were isolated as their triflate salts and were fully characterized by infrared, 1H and 13C NMR spectroscopy, and some representative complexes by single-crystal X-ray structure analysis. The X-ray structures of 3, 5 and 6 confirm the formation of the tetranuclear metalla-cycles, and suggest that complexes 5 and 6 possess a cavity of sufficient size to encapsulate small guest molecules. In addition, the antiproliferative activity of the metalla-cycles 3–8 was evaluated against the human ovarian A2780 (cisplatin sensitive and A2780cisR (cisplatin resistant cancer cell lines and on non-tumorigenic human embryonic kidney HEK293 cells. All cationic tetranuclear metalla-rectangles were found to be highly cytotoxic, with IC50 values in the low micromolar range.

KARAKTERISASI ENZIM POLIFENOL OKSIDASE BIJI KAKAO (Theobroma cacao Linn. Characterization of Polyphenol Oxidase Enzyme of Cocoa Beans (Theobroma cacao Linn.

Directory of Open Access Journals (Sweden)

G.P. Ganda Putra

2012-05-01

max equals to 595,24 U/gram (db of cocoa beans and K equals to 0,20 M; result of SDS- PAGE of enzyme shows protein bands at M� of 11,75; 17,80; 27,80; 36,03 and 131,52 kDa; and finally, optimumcondition of enzyme activity is at the temperature of 53,43oC; pH 5,42 and incubation time of 80,91 minutes. ABSTRAK Telah dilakukan penelitian dengan tujuan untuk: (1 mengetahui karakteristik enzim polifenol oksidase dan (2 menen- tukan kondisi (suhu, pH dan waktu inkubasi optimum aktivitas enzim polifenol oksidase, yang diisolasi dari biji kakao kering. Hasil penelitian berupa kondisi (suhu, pH dan waktu inkubasi optimum aktivitas enzim polifenol oksidase akan diaplikasikan untuk perbaikan mutu biji kakao kering melalui teknik rehidrasi. Penelitian ini dilakukan melalui tahapan: (1 isolasi enzim polifenol oksidase dari 10 sampel biji kakao kering di Provinsi Bali, (2 karakterisasi enzim polifenol oksidase (aktivitas, kinetika enzim, BM dan (3 penentuan kondisi suhu, pH dan waktu inkubasi optimum. Hasil yang diperoleh menunjukkan bahwa: (1 aktivitas enzim polifenol oksidase rata-rata 157,49 ± 58,03 U/gram (bk biji kakao dengan aktivitas maksimum 258,22 U/gram (bk biji kakao dan minimum 59,01 U/gram (bk biji kakao; maks sebesar 595,24 U/gram (bk biji kakao dan K sebesar 0,20 M; hasil SDS-PAGE enzim menunjukkan pita-pita protein yang terbentuk pada BM 11,75; 17,80; 27,80; 36,03 dan 131,52 kDa; dan (2 kondisi optimum aktivitas enzimadalah suhu 53,43oC; pH 5,42 dan waktu inkubasi 80,91 menit.

Twitter.com kā korporatīvo sabiedrisko attiecību instruments Latvijā: satura analīze

OpenAIRE

Lulle, Katrīna

2010-01-01

Bakalaura darba tēma ir „Twitter.com kā korporatīvo sabiedrisko attiecību instruments Latvijā: satura analīze”. Darba ietvaros analizēti 10 Latvijas uzľēmumu Twitter.com profilu ieraksti laika periodā no 2009. gada decembra līdz 2010. gada februārim, kopumā 2780 ieraksti. Darba mērķis ir veikt Latvijas uzľēmumu Twitter.com profilu satura analīzi, lai noteiktu, kā Twitter.com tiek izmantots kā korporatīvo sabiedrisko attiecību instruments. Darbā ir divas teorētiskās nodaļas par sabied...

Methanol adsorption on Pt(111)

International Nuclear Information System (INIS)

Melo, A.V.; Chottiner, G.S.; Hoffman, R.W.; O'Grady, W.E.

1984-12-01

High resolution electron energy loss spectroscopy has been used to study the decomposition of methanol on a Pt(111) surface. Several intermediate states in the decomposition are identified by quenching the sample when reactions occur. At 100 K a set of peaks at 800, 1040, 1350, and 2890 cm -1 indicates the presence of a multilayer molecularly adsorbed methanol. As the sample is warmed to 130 K peaks develop at 1700 and 2780 cm -1 , suggesting the formation of formaldehyde on the surface. With further heating, peaks grow at 1820 and 2560 cm -1 due to the formation of a formyl species during the decomposition of methanol over Pt(111). Further heating leads to the final conversion of the surface species to adsorbed CO and carbonaceous residues

Optically pumped FIR lasers and their application in plasma diagnostics

International Nuclear Information System (INIS)

Bakos, J.S.

1986-06-01

The pysics and the construction of the far infrared lasers (FIRL) and of the infrared lasers pumping them are reviewed. The details of the construction, resonating and pumping systems, spectral and power characteristics of the FIRLs are discussed. Recently more than 1000 laser lines are known and used in the 27-80 mm wavelength range, but in many cases the laser kinetics are not fully understood, and some instability phenomena cannot be prevented. New nonlinear processes were found: two-photon pumping, hyper Raman laser tuning and relaxation phenomena. A broad application field, the plasma diagnostics by far infrared lasers is described. Scattering of infrared laser radiation can give new interesting information on the not understood effect of the anomalous transport in the high temperature plasma. (D.Gy.)

Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

LENUS (Irish Health Repository)

Furlong, Fiona

2012-04-01

Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3\\' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3\\'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3\\' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

Gold(III) complexes with 2-substituted pyridines as experimental anticancer agents: solution behavior, reactions with model proteins, antiproliferative properties.

Science.gov (United States)

Maiore, Laura; Cinellu, Maria Agostina; Nobili, Stefania; Landini, Ida; Mini, Enrico; Gabbiani, Chiara; Messori, Luigi

2012-03-01

Gold(III) compounds form a family of promising cytotoxic and potentially anticancer agents that are currently undergoing intense preclinical investigations. Four recently synthesized and characterized gold(III) derivatives of 2-substituted pyridines are evaluated here for their biological and pharmacological behavior. These include two cationic adducts with 2-pyridinyl-oxazolines, [Au(pyox(R))Cl(2)][PF(6)], [pyox(R)=(S)-4-benzyl-2-(pyridin-2-yl)-4,5-dihydrooxazole, I; (S)-4-iso-propyl-2-(pyridin-2-yl)-4,5-dihydrooxazole, II] and two neutral complexes [Au(N,N'OH)Cl(2)], III, and [Au(N,N',O)Cl], IV, containing the deprotonated ligand N-(1-hydroxy-3-iso-propyl-2-yl)pyridine-2-carboxamide, N,N'H,OH, resulting from ring opening of bound pyox(R) ligand of complex II by hydroxide ions. The solution behavior of these compounds was analyzed. These behave as classical prodrugs: activation of the metal center typically takes place through release of the labile chloride ligands while the rest of the molecule is not altered; alternatively, activation may occur through gold(III) reduction. All compounds react eagerly with the model protein cyt c leading to extensive protein metalation. ESI MS experiments revealed details of gold-cyt c interactions and allowed us to establish the nature of protein bound metal containing fragments. The different behavior displayed by I and II compared to III and IV is highlighted. Remarkable cytotoxic properties, against the reference human ovarian carcinoma cell lines A2780/S and A2780/R were disclosed for all tested compounds with IC(50) values ranging from 1.43 to 6.18 μM in the sensitive cell line and from 1.59 to 10.86 μM in the resistant one. The common ability of these compounds to overcome cisplatin resistance is highlighted. The obtained results are thoroughly discussed in the frame of current knowledge on cytotoxic gold compounds. Copyright © 2011 Elsevier Inc. All rights reserved.

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

Science.gov (United States)

Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

2013-09-01

Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p cisplatin complexes resulted in a 7.0-fold increase ( p cisplatin chemotherapy of ovarian cancer.

Making a commercial carbon fiber cloth having comparable capacitances to carbon nanotubes and graphene in supercapacitors through a "top-down" approach.

Science.gov (United States)

Zhang, Tianchang; Kim, Christine H J; Cheng, Yingwen; Ma, Yanwen; Zhang, Hongbo; Liu, Jie

2015-02-21

A "top-down" and scalable approach for processing carbon fiber cloth (CFC) into flexible and all-carbon electrodes with remarkable areal capacity and cyclic stability was developed. CFC is commercially available in large quantities but its use as an electrode material in supercapacitors is not satisfactory. The approach demonstrated in this work is based on the sequential treatment of CFC with KOH activation and high temperature annealing that can effectively improve its specific surface area to a remarkable 2780 m(2) g(-1) while at the same time achieving a good electrical conductivity of 320 S m(-1) without sacrificing its intrinsic mechanical strength and flexibility. The processed CFC can be directly used as an electrode for supercapacitors without any binders, conductive additives and current collectors while avoiding elaborate electrode processing steps to deliver a specific capacitance of ∼0.5 F cm(-2) and ∼197 F g(-1) with remarkable rate performance and excellent cyclic stability. The properties of these processed CFCs are comparable or better than graphene and carbon nanotube based electrodes. We further demonstrate symmetric solid-state supercapacitors based on these processed CFCs with very good flexibility. This "top-down" and scalable approach can be readily applied to other types of commercially available carbon materials and therefore can have a substantial significance for high performance supercapacitor devices.

Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors.

Science.gov (United States)

Burger, Matthew T; Knapp, Mark; Wagman, Allan; Ni, Zhi-Jie; Hendrickson, Thomas; Atallah, Gordana; Zhang, Yanchen; Frazier, Kelly; Verhagen, Joelle; Pfister, Keith; Ng, Simon; Smith, Aaron; Bartulis, Sarah; Merrit, Hanne; Weismann, Marion; Xin, Xiaohua; Haznedar, Joshua; Voliva, Charles F; Iwanowicz, Ed; Pecchi, Sabina

2011-01-13

Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure-guided optimization of these pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties. A series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently inhibit PI3K, were discovered. Within this series a compound, 17, was identified with suitable pharmacokinetic (PK) properties, which allowed for the establishment of a PI3K PK/pharmacodynamic-efficacy relationship as determined by in vivo inhibition of AKT(Ser473) phosphorylation and tumor growth inhibition in a mouse A2780 tumor xenograft model.

Characterization of Taurine Transporting Systems During Acquirement of Resistance to Platinum(II)-based, Chemotherapeutic Drugs

DEFF Research Database (Denmark)

Sørensen, Belinda Halling

Although, cisplatin is one of the most effective broad-spectrum anticancer drugs, prolonged cisplatin treatment often results in development of chemoresistance and subsequent therapeutic failure. Dysregulation of the taurine transporting systems i.e., the taurine transporter (TauT) and volume....... Cisplatin resistance correlates with a reduction in the volume regulated anion current and taurine release mediated by VRACs, as well as an improved cellular accumulation of taurine through TauT. In human ovarian A2780 cancer cells, for instance, cisplatin resistance is associated with an absent swelling......-induced taurine release and inability to volume regulate. The dismissed taurine release was due to an almost absent leucin-rich-repeat containing 8A (LRRC8A) total protein expression. LRRC8A is an important component of VRACs. Cellular taurine contributes to the intracellular pool of organic osmolytes. Moreover...

Risk assessment, spatial distribution, and source apportionment of heavy metals in Chinese surface soils from a typically tobacco cultivated area.

Science.gov (United States)

Liu, Haiwei; Wang, Haiyun; Zhang, Yan; Yuan, Jumin; Peng, Yaodong; Li, Xiuchun; Shi, Yi; He, Kuanxin; Zhang, Qiming

2018-06-01

The heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in the surface soils of tobacco (Nicotiana tabacum L.) fields in Jiangxi Province were analyzed, and the mean heavy metal concentrations were 3.55, 0.19, 25.89, 14.96, 0.25, 10.89, 27.80, and 44.00 mg/kg, respectively. Spatial distribution analysis showed that the highest concentrations were recorded in the north-western, south-western, and mid-eastern parts of the study area. The index of geo-accumulation and pollution index indicated modest enrichment with Cd and Hg, which were the only two metals posing a potentially high ecological risk to the local agricultural environment. The health risk assessment showed no considerable non-carcinogenic or carcinogenic risks for children and adults from these elements. The principal component analysis (PCA) and cluster analysis (CA) found that the variations in the Cr and Ni concentrations were largely on account of the soil parent rocks, but the As, Cd, Cu, and Hg variations in the soil were largely owing to agricultural practices of years. However, the main factor influencing Pb and Zn was atmospheric deposition.

Heterogeneous Photo catalytic Degradation of Hazardous Waste in Aqueous Suspension

International Nuclear Information System (INIS)

Sadek, S.A.; Ebraheem, S.; Friesen, K.J.

1999-01-01

The photo catalytic degradation of hazardous waste like chlorinated paraffin compound (1,12-Dichlorodoecane Ded) was investigated in different aquatic media using GC-MSD. The direct photolysis of Ded in HPLC water was considered to be negligible (k = 0.0020+-0.0007h - 1 ) . An acceleration of the photodegradation rate was occurred in presence of different TiO 2 catalyst systems. Molecular oxygen was found to play a vital role in the degradation process. Anatase TiO 2 was proved to be the most efficient one (k=0.7670+-0.0876h -1 ), while the rate constant of the rutile TiO 2 was calculated to be 0.2780+-0.0342h -1 . Improvement of photo catalytic efficiency of rutile TiO 2 was achieved by addition of Fe +2 giving a rate constant =0.6710+-0.0786h -1

Revealing the Cytotoxicity of Residues of Phosphazene Catalysts Used for Synthesis of Poly(ethylene oxide)

KAUST Repository

Xia, Yening

2017-08-24

We herein report a case study on the toxicity of residual catalyst in metal-free polymer. Eight-arm star-like poly(ethylene oxide)s were successfully synthesized via phosphazene-catalyzed ring-opening polymerization of ethylene oxide using sucrose as an octahydroxy initiator. The products were subjected to MTT assay using human cancer cell lines (MDA-MB-231 and A2780). Comparison between the crude and purified products clearly revealed that the residual phosphazenium salts were considerably cytotoxic regardless of the anionic species, and that the cytotoxicity of more bulky t-BuP4 salt was higher than that of t-BuP2 salt. Such results have therefore put forward the necessity for removal of the catalyst residues from PEO-based polymers synthesized through phosphazene catalysis for bio-related applications, and for the development of less or non-toxic organocatalysts for such polymers.

Revealing the Cytotoxicity of Residues of Phosphazene Catalysts Used for Synthesis of Poly(ethylene oxide)

KAUST Repository

Xia, Yening; Shen, Jizhou; Alamri, Haleema; Hadjichristidis, Nikolaos; Zhao, Junpeng; Wang, Yucai; Zhang, Guangzhao

2017-01-01

We herein report a case study on the toxicity of residual catalyst in metal-free polymer. Eight-arm star-like poly(ethylene oxide)s were successfully synthesized via phosphazene-catalyzed ring-opening polymerization of ethylene oxide using sucrose as an octahydroxy initiator. The products were subjected to MTT assay using human cancer cell lines (MDA-MB-231 and A2780). Comparison between the crude and purified products clearly revealed that the residual phosphazenium salts were considerably cytotoxic regardless of the anionic species, and that the cytotoxicity of more bulky t-BuP4 salt was higher than that of t-BuP2 salt. Such results have therefore put forward the necessity for removal of the catalyst residues from PEO-based polymers synthesized through phosphazene catalysis for bio-related applications, and for the development of less or non-toxic organocatalysts for such polymers.

Leaf curl diseases of two solanaceous species in Southwest Arabia are caused by a monopartite begomovirus evolutionarily most closely related to a species from the Nile Basin and unique suite of betasatellites

KAUST Repository

Idris, Ali

2012-10-01

The complete genome of 2780 bases was amplified using rolling circle amplification, and cloned, and sequenced for two distinct strains of the monopartite begomovirus Tomato leaf curl Sudan virus (ToLCSDV). The two strains shared 86-91% identity with the previously described ToLCSDV from the Nile Basin, and 90-91% identity with one another. One strain was cloned from symptomatic tomato plants from Tihamah (ToLCSDV-YE[YE:Tih:05]) while the other was cloned from symptomatic tobacco plants collected from Wadi Hadramaut (ToLCSDV-YE[YE:Had:89]). A distinct full-length betasatellite molecule (1352 bases) was cloned from the respective field-infected tomato and tobacco plants. Agro-inoculation of tomato and Nicotiana benthamiana plants with cloned partial tandem repeats of ToLCSDV-YE[YE:Tih11:05]) and the associated betasatellite, Tomato leaf curl Yemen betasatellite (ToLCYEB-[Tih:tom:137:05]), resulted in the reproduction of leaf curl disease symptoms in test plants like those observed in the field-infected plants. The betasatellite contributed to symptom severity in N. benthamiana test plants when it was co-inoculated with ToLCSDV-YE, compared to the milder symptoms that were observed in tobacco plants infected with the helper virus alone. © 2012 Elsevier B.V.

Leaf curl diseases of two solanaceous species in Southwest Arabia are caused by a monopartite begomovirus evolutionarily most closely related to a species from the Nile Basin and unique suite of betasatellites

KAUST Repository

Idris, Ali; Abdullah, N.; Brown, Judith K.

2012-01-01

The complete genome of 2780 bases was amplified using rolling circle amplification, and cloned, and sequenced for two distinct strains of the monopartite begomovirus Tomato leaf curl Sudan virus (ToLCSDV). The two strains shared 86-91% identity with the previously described ToLCSDV from the Nile Basin, and 90-91% identity with one another. One strain was cloned from symptomatic tomato plants from Tihamah (ToLCSDV-YE[YE:Tih:05]) while the other was cloned from symptomatic tobacco plants collected from Wadi Hadramaut (ToLCSDV-YE[YE:Had:89]). A distinct full-length betasatellite molecule (1352 bases) was cloned from the respective field-infected tomato and tobacco plants. Agro-inoculation of tomato and Nicotiana benthamiana plants with cloned partial tandem repeats of ToLCSDV-YE[YE:Tih11:05]) and the associated betasatellite, Tomato leaf curl Yemen betasatellite (ToLCYEB-[Tih:tom:137:05]), resulted in the reproduction of leaf curl disease symptoms in test plants like those observed in the field-infected plants. The betasatellite contributed to symptom severity in N. benthamiana test plants when it was co-inoculated with ToLCSDV-YE, compared to the milder symptoms that were observed in tobacco plants infected with the helper virus alone. © 2012 Elsevier B.V.

Quantitative estimation of itopride hydrochloride and rabeprazole sodium from capsule formulation.

Science.gov (United States)

Pillai, S; Singhvi, I

2008-09-01

Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C(18) column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies.

Measurement of nitrogen in the body using a commercial PGNAA system--phantom experiments.

Science.gov (United States)

Chichester, D L; Empey, E

2004-01-01

An industrial prompt-gamma neutron activation analysis (PGNAA) system, originally designed for the real-time elemental analyses of bulk coal on a conveyor belt, has been studied to examine the feasibility of using such a system for body composition analysis. Experiments were conducted to measure nitrogen in a simple, tissue equivalent phantom comprised of 2.7 wt% of nitrogen. The neutron source for these experiments was 365 MBq (18.38 microg) of 252Cf located within an engineered low Z moderator and it yielded a dose rate in the measurement position of 3.91 mSv/h; data were collected using a 2780 cm(3) NaI(Tl) cylindrical detector with a digital signal processor and a 512 channel MCA. Source, moderator and detector geometries were unaltered from the system's standard configuration, where they have been optimized for considerations such as neutron thermalization, measurement sensitivity and uniformity, background radiation and external dose minimization. Based on net counts in the 10.8 MeV PGNAA nitrogen photopeak and its escape peaks the dose dependent nitrogen count rate was 11,600 counts/mSv with an uncertainty of 3.0% after 0.32 mSv (4.9 min), 2.0% after 0.74 mSv (11.4 min) and 1.0% after 3.02 mSv (46.4 min).

Niosome Encapsulation of Curcumin: Characterization and Cytotoxic Effect on Ovarian Cancer Cells

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Ying-Qi Xu

2016-01-01

Full Text Available Curcumin, a natural chemical compound found in Curcuma longa, has been applied in multiple medicinal areas from antibiotic to antitumor treatment. However, the chemical structure of curcumin results in poor stability, low solubility, and rapid degradation in vivo, hindering its clinical utilization. To address these issues, we have developed a novel niosome system composed of nonionic surfactants: Span 80, Tween 80, and Poloxamer 188. Curcumin was encapsulated in the niosomes with a high entrapment efficiency of 92.3±0.4%. This system provided controlled release of curcumin, thereby improving its therapeutic capability. Dynamic dialysis was conducted to evaluate the in vitro drug release of curcumin-niosomes. Curcumin-niosomes exhibited enhanced cytotoxic activity and apoptotic rate against ovarian cancer A2780 cells compared with freely dispersed curcumin. These results demonstrate that the curcumin-niosome system is a promising strategy for the delivery of curcumin and ovarian cancer therapy.

Cytotoxic cassaine diterpenoid-diterpenoid amide dimers and diterpenoid amides from the leaves of Erythrophleum fordii.

Science.gov (United States)

Du, Dan; Qu, Jing; Wang, Jia-Ming; Yu, Shi-Shan; Chen, Xiao-Guang; Xu, Song; Ma, Shuang-Gang; Li, Yong; Ding, Guang-Zhi; Fang, Lei

2010-10-01

Detailed phytochemical investigation from the leaves of Erythrophleum fordii resulted in the isolation of 13 compounds, including three cassaine diterpenoid-diterpenoid amide dimers (1, 3 and 5), and seven cassaine diterpenoid amides (6 and 8-13), together with three previously reported ones, erythrophlesins D (2), C (4) and 3beta-hydroxynorerythrosuamide (7). Compounds 1, 3 and 5 are further additions to the small group of cassaine diterpenoid dimers represented by erythrophlesins A-D. Their structures were determined by analysis of extensive one- and two-dimensional NMR experiments and ESIMS methods. Cytotoxic activities of the isolated compounds were tested against HCT-8, Bel-7402, BGC-823, A549 and A2780 human cancer cell lines in the MTT test. Results showed that compounds 1 and 3-5 exhibited significantly selective cytotoxic activities (IC(50)<10 microM) against these cells, respectively. Copyright © 2010 Elsevier Ltd. All rights reserved.

Identification and characterization of SSE15206, a microtubule depolymerizing agent that overcomes multidrug resistance

KAUST Repository

Manzoor, Safia

2018-02-13

Microtubules are highly dynamic structures that form spindle fibres during mitosis and are one of the most validated cancer targets. The success of drugs targeting microtubules, however, is often limited by the development of multidrug resistance. Here we describe the discovery and characterization of SSE15206, a pyrazolinethioamide derivative [3-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide] that has potent antiproliferative activities in cancer cell lines of different origins and overcomes resistance to microtubule-targeting agents. Treatment of cells with SSE15206 causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation, a phenotype often associated with drugs that interfere with microtubule dynamics. SSE15206 inhibits microtubule polymerization both in biochemical and cellular assays by binding to colchicine site in tubulin as shown by docking and competition studies. Prolonged treatment of cells with the compound results in apoptotic cell death [increased Poly (ADP-ribose) polymerase cleavage and Annexin V/PI staining] accompanied by p53 induction. More importantly, we demonstrate that SSE15206 is able to overcome resistance to chemotherapeutic drugs in different cancer cell lines including multidrug-resistant KB-V1 and A2780-Pac-Res cell lines overexpressing MDR-1, making it a promising hit for the lead optimization studies to target multidrug resistance.

A Dyadic Perspective on Childhood Maltreatment for Women With Provoked Vestibulodynia and Their Partners: Associations With Pain and Sexual and Psychosocial Functioning.

Science.gov (United States)

Corsini-Munt, Serena; Bergeron, Sophie; Rosen, Natalie O; Beaulieu, Noémie; Steben, Marc

2017-01-01

Childhood maltreatment is robustly associated with adult-onset vulvodynia, a common form of female genito-pelvic pain/penetration disorder. However, little is known about the impact of childhood maltreatment on current sexual, psychological, and relationship adaptation for couples with provoked vestibulodynia (PVD). This study examined the associations between childhood maltreatment and sexual and psychosocial functioning and pain in women with PVD, the most common subtype of vulvodynia, and their partners. A total of 49 couples (M age women = 27.80, SD = 6.05; M age men = 30.04; SD = 6.48) with PVD completed the Childhood Trauma Questionnaire (CTQ), as well as measures of sexual functioning, couple satisfaction, and anxiety. Women also reported on their pain during intercourse. Analyses were guided by the actor-partner interdependence model. Women's higher reports of childhood maltreatment were associated with their lower sexual functioning and higher anxiety. Partners' higher reports of childhood maltreatment were associated with their lower sexual functioning, lower couple satisfaction, and higher anxiety, as well as women's lower couple satisfaction and higher anxiety. Both women's and partners' higher reports of childhood maltreatment were associated with higher affective pain for women. Findings suggest childhood maltreatment experienced by women with PVD and their partners should be considered as part of treatment planning.

Excision of oral mucocele by different wavelength lasers

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Umberto Romeo

2013-01-01

Full Text Available Background: Mucocele is a common benign neoplasm of oral soft tissues and the most common after fibroma. It generally occurs in the lower lip and its treatment includes excision of cyst and the responsible salivary gland, in order to prevent recurrences. Aims: To evaluate the capability of three different lasers in performing the excision of labial mucocele with two different techniques. Materials and Methods: In the presented cases, excision was performed using two different techniques (circumferential incision technique and mucosal preservation technique and three different laser wavelengths (Er,Cr:YSGG 2780 nm, diode 808 nm, and KTP 532 nm. Results: All the tested lasers, regardless of wavelength, showed many advantages (bloodless surgical field, no postoperative pain, relative speed, and easy execution. The most useful surgical technique depends on clinical features of the lesion. Conclusion: Tested lasers, with both techniques, are helpful in the management of labial mucocele.

Role of complex utilization of mineral raw materials In geological research

Energy Technology Data Exchange (ETDEWEB)

Takacs, P.; Varju, G.

1979-01-01

Presents Hungarian research efforts on ways of utilizing the secondary raw materials alunite, pumice and slate coal from various mines. The slate coal is separated from brown coal and disposed of at spoil banks of brown coal mines, due to its high ash content (up to 56.8% under dry conditions), silicate content up to 58.2% and low calorific value between 1500 and 2780 kcal/kg. The research proposal for utilizing slate coal is directed at partial separation of the mineral and coal content by comminution, peptization and hydrocentrifugal separation. The larger part of the silicate content is held in the colloid suspension, which could be used for conditioning drilling mud or foundry sand. The produced coal concentrate has a reduced ash content and higher calorific value (between 500 and 800 kcal/kg) and could be employed in soil amelioration or combustion. (10 refs.) (In German)

Welding, a risk factor of lung cancer: the ICARE study.

Science.gov (United States)

Matrat, Mireille; Guida, Florence; Mattei, Francesca; Cénée, Sylvie; Cyr, Diane; Févotte, Joëlle; Sanchez, Marie; Menvielle, Gwenn; Radoï, Loredana; Schmaus, Annie; Woronoff, Anne-Sophie; Luce, Danièle; Stücker, Isabelle

2016-04-01

We investigated the relationship between lung cancer and occupational exposure to welding activity in ICARE, a population-based case-control study. Analyses were restricted to men (2276 cases, 2780 controls). Welding exposure was assessed through detailed questionnaires, including lifelong occupational history. ORs were computed using unconditional logistic regression, adjusted for lifelong cigarette smoking and occupational exposure to asbestos. Among the regular welders, welding was associated with a risk of lung cancer (OR=1.7, 95% CI 1.1 to 2.5), which increased with the duration (OR=2.0, 95% CI 1.0 to 3.9 when duration >10 years), and was maximum 10-20 years since last welding. The risk was more pronounced in case of gas welding (OR=2.0, 95% CI 1.2 to 3.3), when the workpiece was covered by paint, grease, or other substances (OR=2.0, 95% CI 1.2 to 3.4) and when it was cleaned with chemical substances before welding. No statistically significant increase in lung cancer risk was observed among occasional welders. Although these results should be confirmed, we showed that type of welding and mode of workpiece preparation are important determinants of the lung cancer risk in regular welders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Contributions of mobile, stationary and biogenic sources to air pollution in the Amazon rainforest: a numerical study with the WRF-Chem model

Science.gov (United States)

Abou Rafee, Sameh A.; Martins, Leila D.; Kawashima, Ana B.; Almeida, Daniela S.; Morais, Marcos V. B.; Souza, Rita V. A.; Oliveira, Maria B. L.; Souza, Rodrigo A. F.; Medeiros, Adan S. S.; Urbina, Viviana; Freitas, Edmilson D.; Martin, Scot T.; Martins, Jorge A.

2017-06-01

This paper evaluates the contributions of the emissions from mobile, stationary and biogenic sources on air pollution in the Amazon rainforest by using the Weather Research and Forecasting with Chemistry (WRF-Chem) model. The analyzed air pollutants were CO, NOx, SO2, O3, PM2. 5, PM10 and volatile organic compounds (VOCs). Five scenarios were defined in order to evaluate the emissions by biogenic, mobile and stationary sources, as well as a future scenario to assess the potential air quality impact of doubled anthropogenic emissions. The stationary sources explain the highest concentrations for all air pollutants evaluated, except for CO, for which the mobile sources are predominant. The anthropogenic sources considered resulted an increasing in the spatial peak-temporal average concentrations of pollutants in 3 to 2780 times in relation to those with only biogenic sources. The future scenario showed an increase in the range of 3 to 62 % in average concentrations and 45 to 109 % in peak concentrations depending on the pollutant. In addition, the spatial distributions of the scenarios has shown that the air pollution plume from the city of Manaus is predominantly transported west and southwest, and it can reach hundreds of kilometers in length.

Contributions of mobile, stationary and biogenic sources to air pollution in the Amazon rainforest: a numerical study with the WRF-Chem model

Directory of Open Access Journals (Sweden)

S. A. Abou Rafee

2017-06-01

Full Text Available This paper evaluates the contributions of the emissions from mobile, stationary and biogenic sources on air pollution in the Amazon rainforest by using the Weather Research and Forecasting with Chemistry (WRF-Chem model. The analyzed air pollutants were CO, NOx, SO2, O3, PM2. 5, PM10 and volatile organic compounds (VOCs. Five scenarios were defined in order to evaluate the emissions by biogenic, mobile and stationary sources, as well as a future scenario to assess the potential air quality impact of doubled anthropogenic emissions. The stationary sources explain the highest concentrations for all air pollutants evaluated, except for CO, for which the mobile sources are predominant. The anthropogenic sources considered resulted an increasing in the spatial peak-temporal average concentrations of pollutants in 3 to 2780 times in relation to those with only biogenic sources. The future scenario showed an increase in the range of 3 to 62 % in average concentrations and 45 to 109 % in peak concentrations depending on the pollutant. In addition, the spatial distributions of the scenarios has shown that the air pollution plume from the city of Manaus is predominantly transported west and southwest, and it can reach hundreds of kilometers in length.

Particle-in-cell Simulations of Raman Laser Amplification in Ionizing Plasmas

International Nuclear Information System (INIS)

Clark, Daniel S.; Fisch, Nathaniel J.

2003-01-01

By using the amplifying laser pulse in a plasma-based backward Raman laser amplifier to generate the plasma by photo-ionization of a gas simultaneous with the amplification process, possible instabilities of the pumping laser pulse can be avoided. Particle-in-cell simulations are used to study this amplification mechanism, and earlier results using more elementary models of the Raman interaction are verified [D.S. Clark and N.J. Fisch, Phys. Plasmas, 9 (6): 2772-2780, 2002]. The effects (unique to amplification in ionizing plasmas and not included in previous simulations) of blue-shifting of the pump and seed laser pulses and the generation of a wake are observed not significantly to impact the amplification process. As expected theoretically, the peak output intensity is found to be limited to I ∼ 10 17 W/cm 2 by forward Raman scattering of the amplifying seed. The integrity of the ionization front of the seed pulse against the development of a possible transverse modulation instability is also demonstrated

Evaluation of zeolite mixtures for decontaminating high-activity-level water at the Three Mile Island Unit 2 Nuclear Power Station

International Nuclear Information System (INIS)

Collins, E.D.; Campbell, D.O.; King, L.J.; Knauer, J.B.; Wallace, R.M.

1984-05-01

Mixtures of Linde Ionsiv IE-96 and Ionsiv A-51 were evaluated for use in the Submerged Demineralizer System (SDS) that was installed at the Three Mile Island Unit 2 Nuclear Power Station to decontaminate approx. 2780 m 3 of high-activity-level water. The original SDS flowsheet was conservatively designed for removal of cesium and strontium and would have required the use of approx. 60 SDS columns. Mixed zeolite tests were made on a 10 -5 scale and indicated that the appropriate ratio of IE-96/A-51 was 3/2. A mathematical model was used to predict the performance of the mixed zeolite columns in the SDS configuration and with the intended method of operation. Actual loading results were similar to those predicted for strontium and better than those predicted for cesium. The number of SDS columns needed to process the HALW was reduced to approx. 10. 6 references, 4 figures, 2 tables

Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents.

Science.gov (United States)

Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V; Bronich, Tatiana K

2010-04-12

Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross-linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs.

Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis.

Science.gov (United States)

Karski, Erin E; Matthay, Katherine K; Neuhaus, John M; Goldsby, Robert E; Dubois, Steven G

2013-02-01

The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Patients ≥40 years of age were more likely to have extra-skeletal tumors (66.1% vs. 31.7%; p extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fine mapping of the sunflower resistance locus Pl(ARG) introduced from the wild species Helianthus argophyllus.

Science.gov (United States)

Wieckhorst, S; Bachlava, E; Dussle, C M; Tang, S; Gao, W; Saski, C; Knapp, S J; Schön, C-C; Hahn, V; Bauer, E

2010-11-01

Downy mildew, caused by Plasmopara halstedii, is one of the most destructive diseases in cultivated sunflower (Helianthus annuus L.). The dominant resistance locus Pl(ARG) originates from silverleaf sunflower (H. argophyllus Torrey and Gray) and confers resistance to all known races of P. halstedii. We mapped Pl(ARG) on linkage group (LG) 1 of (cms)HA342 × ARG1575-2, a population consisting of 2,145 F(2) individuals. Further, we identified resistance gene candidates (RGCs) that cosegregated with Pl(ARG) as well as closely linked flanking markers. Markers from the target region were mapped with higher resolution in NDBLOS(sel) × KWS04, a population consisting of 2,780 F(2) individuals that does not segregate for Pl(ARG). A large-insert sunflower bacterial artificial chromosome (BAC) library was screened with overgo probes designed for markers RGC52 and RGC151, which cosegregated with Pl(ARG). Two RGC-containing BAC contigs were anchored to the Pl(ARG) region on LG 1.

Cisplatin Loaded Hyaluronic Acid Modified TiO2 Nanoparticles for Neoadjuvant Chemotherapy of Ovarian Cancer

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Enling Liu

2015-01-01

Full Text Available Novel tumor-targeting titanium dioxide (TiO2 nanoparticles modified with hyaluronic acid (HA were developed to explore the feasibility of exploiting the pH-responsive drug release property of TiO2 and the tumor-targeting ability of HA to construct a tumor-targeting cisplatin (CDDP delivery system (HA-TiO2 for potential neoadjuvant chemotherapy of ovarian cancer. The experimental results indicated that CDDP release from the HA-TiO2 nanoparticles was significantly accelerated by decreasing pH from 7.4 to 5.0, which is of particular benefit to cancer therapy. CDDP-loaded HA-TiO2 nanoparticles increased the accumulation of CDDP in A2780 ovarian cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo real-time imaging assay revealed that HA-TiO2 nanoparticles possessed preferable tumor-targeting ability which might potentially minimize the toxic side effects of CDDP in clinical application.

Eliciting the Intension of Drug Value Sets – Principles and Quality Assurance Applications

Science.gov (United States)

Bahr, Nathan J.; Nelson, Scott D.; Winnenburg, Rainer; Bodenreider, Olivier

2018-01-01

Value sets (VSs) used in electronic clinical quality measures are lists of codes from standard terminologies (“extensional” VSs), whose purpose (“intension”) is not always explicitly stated. We elicited the intension for the 09/01/2014 release of extensional medication value sets by comparison to drug classes from the October 2014 release of RxClass. Value sets matched drug classes if they shared common ingredients, as evidenced by Jaccard similarity score. We elicited the intension of 80 extensional value sets. The average Jaccard similarity was 0.65 for single classes and 0.80 for combination classes, with 34% (27/80) of the value sets having high similarity scores. Manual review by a pharmacist indicated 51% (41/80) of the drug classes selected as the best mapping for a value set matched the intension reflected in that value set name. This approach has the potential for facilitating the development and maintenance of medication value sets. PMID:29295218

New benzimidazoles and their antitumor effects with Aurora A kinase and KSP inhibitory activities.

Science.gov (United States)

Abd El-All, Amira S; Magd-El-Din, Asmaa A; Ragab, Fatma A F; ElHefnawi, Mahmoud; Abdalla, Mohamed M; Galal, Shadia A; El-Rashedy, Ahmed A

2015-07-01

A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and (1) H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A gargantuan acetaminophen level in an acidemic patient treated solely with intravenous N-acetylcysteine.

Science.gov (United States)

Zell-Kanter, Michele; Coleman, Patrick; Whiteley, Patrick M; Leikin, Jerrold B

2013-01-01

The objective of this report is to describe an acidemic patient with one of the largest recorded acetaminophen ingestions in a patient with acidemia who was treated with supportive care and intravenous (IV) N-acetylcysteine. A 59-year-old female with a history of depression was found comatose. In the Emergency Department, she was obtunded with agonal respirations and immediately intubated. Activated charcoal was given through a nasogastric tube. An initial acetaminophen serum level was 1141 mg/L. The patient was started on IV N-acetylcysteine. The acetaminophen level peaked 2 hours later at 1193 mg/L. She was continued on the IV N-acetylcysteine protocol. The next day her aspartate aminotransferase was 3150 U/L, alanine aminotransferase was 2780 U/L, and creatinine phosphokinase was 16,197 U/L. There was no elevation in bilirubin or international normalized ratio (INR). Transaminase levels decreased on day 3 and normalized by day 4 when she was transferred to a psychiatric unit. Few cases have been reported of strikingly elevated acetaminophen levels in poisoned patients who did not receive hemodialysis. These patients did have increased lactate levels, and some had normal liver function tests. All of these patients received N-acetylcysteine and survived the poisoning without sequelae. This patient in this report was unique in that she had the highest reported serum acetaminophen level with acidosis and was treated successfully with only IV N-acetylcysteine and supportive care.

Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

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Yallapu Murali M

2010-04-01

Full Text Available Abstract Background Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. Methods Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid (PLGA nanoparticle formulation of curcumin (Nano-CUR was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. Results Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre

Antiproliferative and Antioxidant Properties of Anthocyanin Rich Extracts from Blueberry and Blackcurrant Juice

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Zoriţa Diaconeasa

2015-01-01

Full Text Available The present study was aimed at evaluating the antiproliferative potential of anthocyanin-rich fractions (ARFs obtained from two commercially available juices (blueberry and blackcurrant juices on three tumor cell lines; B16F10 (murine melanoma, A2780 (ovarian cancer and HeLa (cervical cancer. Individual anthocyanin determination, identification and quantification were done using HPLC-MS. Antioxidant activity of the juices was determined through different mechanism methods such as DPPH and ORAC. For biological testing, the juices were purified through C18 cartridges in order to obtain fractions rich in anthocyanins. The major anthocyanins identified were glycosylated cyanidin derivatives. The antiproliferative activity of the fractions was tested using the MTT assay. The antiproliferative potential of ARF was found to be associated with those bioactive molecules, anthocyanins due to their antioxidant potential. The results obtained indicated that both blueberry and blackcurrants are rich sources of antioxidants including anthocyanins and therefore these fruits are highly recommended for daily consumption to prevent numerous degenerative diseases.

Half-Sandwich Ru(II and Os(II Bathophenanthroline Complexes Containing a Releasable Dichloroacetato Ligand

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Pavel Štarha

2018-02-01

Full Text Available We report on the preparation and thorough characterization of cytotoxic half-sandwich complexes [Ru(η6-pcym(bphen(dca]PF6 (Ru-dca and [Os(η6-pcym(bphen(dca]PF6 (Os-dca containing dichloroacetate(1– (dca as the releasable O-donor ligand bearing its own cytotoxicity; pcym = 1-methyl-4-(propan-2-ylbenzene (p-cymene, bphen = 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline. Complexes Ru-dca and Os-dca hydrolyzed in the water-containing media, which led to the dca ligand release (supported by 1H NMR and electrospray ionization mass spectra. Mass spectrometry studies revealed that complexes Ru-dca and Os-dca do not interact covalently with the model proteins cytochrome c and lysozyme. Both complexes exhibited slightly higher in vitro cytotoxicity (IC50 = 3.5 μM for Ru-dca, and 2.6 μM for Os-dca against the A2780 human ovarian carcinoma cells than cisplatin (IC50 = 5.9 μM, while their toxicity on the healthy human hepatocytes was found to be IC50 = 19.1 μM for Ru-dca and IC50 = 19.7 μM for Os-dca. Despite comparable cytotoxicity of complexes Ru-dca and Os-dca, both the complexes modified the cell cycle, mitochondrial membrane potential, and mitochondrial cytochrome c release by a different way, as revealed by flow cytometry experiments. The obtained results point out the different mechanisms of action between the complexes.

Toxicological study of a new maintenance fluid, Veen 3G, in rats.

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Kamei, J; Onodera, K; Kawaguchi, M; Shibata, M; Kagawa, M; Wachi, M; Kojima, J

2002-10-01

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

Indoor Air Quality and Thermal Conditions in a Primary School with a Green Roof System

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Nikolaos Barmparesos

2018-02-01

Full Text Available This paper presents experimental results from a typical school building in Athens, equipped partly with a green roof system (GRS. Environmental monitoring took place in six classrooms located both under the concrete roof and the GRS sectors as well as in the immediate external environment during the warm and cold periods of a school year. Daily measurements of pollutants CO2, TVOCs (Total Volatile Organic Compound, PM1, PM2.5, and PM10 were performed in selected classes. Moreover, indoor ambient temperature (T and relative humidity (RH measurements were implemented in order to estimate the absolute humidity (AH and assess the indoor environmental conditions. The results highlight that during summer, the GRS reduces temperature in a classroom on the top floor by about 2.8 °C, in comparison with the respective classroom under the concrete roof and that AH remained relatively stable for both classrooms. Amid winter, a reverse behavior occurs only for temperature. Moreover, air exchange rates (AER were calculated by using the CO2 decay method for all of the classrooms. The results demonstrated insufficient ventilation for all experimental sights. Finally, concentrations of PM1, PM2.5 and PM10, were found to be relatively decreased, with average values of 0.79, 3.39, and 27.80 μg m−3. Levels of CO2 and TVOCs were elevated during class hours ranging from 469 to 779 ppm and from 6.63 ppm to 13.33 ppm, respectively, but generally within the respective limits of exposure. The examination of the indoor/outdoor (I/O ratio of air pollutants, demonstrated that the outdoor meteorology affects only PM1 and PM2.5, as PM10 and TVOCs are strongly affected by internal sources and the activities of pupils.

Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption.

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R Bartholomé

Full Text Available The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i part of the paracetamol may leave the stomach much quicker than the meal and (ii part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying.ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780.

Sesquiterpenes from Neurolaena lobata and their antiproliferative and anti-inflammatory activities.

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Lajter, Ildikó; Vasas, Andrea; Béni, Zoltán; Forgo, Peter; Binder, Markus; Bochkov, Valery; Zupkó, István; Krupitza, Georg; Frisch, Richard; Kopp, Brigitte; Hohmann, Judit

2014-03-28

Five new sesquiterpenes, neurolobatin A (1), neurolobatin B (2), 5β-hydroxy-8β-isovaleroyloxy-9α-hydroxycalyculatolide (3), 3-epi-desacetylisovaleroylheliangine (4), and 3β-acetoxy-8β-isovaleroyloxyreynosin (5), were isolated from the aerial parts of Neurolaena lobata. The structures were established by means of a combined spectroscopic data analysis, including ESIMS, APCI-MS, and 1D- and 2D-NMR techniques. Neurolobatin A (1) and B (2) are unusual isomeric seco-germacranolide sesquiterpenes with a bicyclic acetal moiety, compounds 3 and 4 are unsaturated epoxy-germacranolide esters, and compound 5 is the first eudesmanolide isolated from the genus Neurolaena. The isolated compounds (1-5) were shown to have noteworthy antiproliferative activities against human tumor cell lines (A2780, A431, HeLa, and MCF7). The anti-inflammatory effects of 1-5, evaluated in vitro using LPS- and TNF-α-induced IL-8 expression inhibitory assays, revealed that all these compounds strongly down-regulated the LPS-induced production of IL-8 protein, with neurolobatin B (2) and 3-epi-desacetylisovaleroylheliangine (4) being the most effective.

Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate.

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Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B; Fuxe, Jonas; Shoshan, Maria

2012-12-01

Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations.

Targeting Gallium to Cancer Cells through the Folate Receptor

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Nerissa Viola-Villegas

2008-01-01

Full Text Available The development of gallium(III compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA with long chain liquid polymer poly(ethylene glycol (PEG 'spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N, N′, N′, N′′-tetraacetic acid (DOTA through amide linkages for delivery into target cells overexpressing the folate receptor (FR. In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4.

Targeting Gallium to Cancer Cells through the Folate Receptor

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Nerissa Viola-Villegas

2008-01-01

Full Text Available The development of gallium(III compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA with long chain liquid polymer poly(ethylene glycol (PEG ‘spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA through amide linkages for delivery into target cells overexpressing the folate receptor (FR. In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4.

Pain Flare Is a Common Adverse Event in Steroid-Naïve Patients After Spine Stereotactic Body Radiation Therapy: A Prospective Clinical Trial

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Chiang, Andrew [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Zeng, Liang; Zhang, Liying; Lochray, Fiona; Korol, Renee; Loblaw, Andrew; Chow, Edward [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada)

2013-07-15

Purpose: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. Methods and Materials: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. Results: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). Conclusions: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells.

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Zhou, Yuanyuan; Zheng, Xia; Lu, Jiaojiao; Chen, Wei; Li, Xu; Zhao, Le

2018-01-01

The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production. Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host

p21 promotes oncolytic adenoviral activity in ovarian cancer and is a potential biomarker

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Lockley Michelle

2010-07-01

Full Text Available Abstract The oncolytic adenovirus dl922-947 replicates selectively within and lyses cells with a dysregulated Rb pathway, a finding seen in > 90% human cancers. dl922-947 is more potent than wild type adenovirus and the E1B-deletion mutant dl1520 (Onyx-015. We wished to determine which host cell factors influence cytotoxicity. SV40 large T-transformed MRC5-VA cells are 3-logs more sensitive to dl922-947 than isogenic parental MRC5 cells, confirming that an abnormal G1/S checkpoint increases viral efficacy. The sensitivity of ovarian cancer cells to dl922-947 varied widely: IC50 values ranged from 51 (SKOV3ip1 to 0.03 pfu/cell (TOV21G. Cells sensitive to dl922-947 had higher S phase populations and supported earlier E1A expression. Cytotoxicity correlated poorly with both infectivity and replication, but well with expression of p21 by microarray and western blot analyses. Matched p21+/+ and -/- Hct116 cells confirmed that p21 influences dl922-947 activity in vitro and in vivo. siRNA-mediated p21 knockdown in sensitive TOV21G cells decreases E1A expression and viral cytotoxicity, whilst expression of p21 in resistant A2780CP cells increases virus activity in vitro and in intraperitoneal xenografts. These results highlight that host cell factors beyond simple infectivity can influence the efficacy of oncolytic adenoviruses. p21 expression may be an important biomarker of response in clinical trials.

Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

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Dehelean Cristina A

2012-11-01

Full Text Available Abstract Background Pentacyclic triterpenes, mainly betulin and betulinic acid, are valuable anticancer agents found in the bark of birch tree. This study evaluates birch bark extracts for the active principles composition. Results New improved extraction methods were applied on the bark of Betula pendula in order to reach the maximum content in active principles. Extracts were analyzed by HPLC-MS, Raman, SERS and 13C NMR spectroscopy which revealed a very high yield of betulin (over 90%. Growth inhibiting effects were measured in vitro on four malignant human cell lines: A431 (skin epidermoid carcinoma, A2780 (ovarian carcinoma, HeLa (cervix adenocarcinoma and MCF7 (breast adenocarcinoma, by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice. Conclusions The research revealed the efficacy of the extraction procedures as well as the antiproliferative and anti-inflammatory effects of birch extracts.

Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities

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Chi-Ming Lee

2013-01-01

Full Text Available Rutaecarpine (RUT, the major bioactive ingredient isolated from the Chinese herb Evodia rutaecarpa, possesses a wide spectrum of biological activities, including anti-inflammation and preventing cardiovascular diseases. However, its high cytotoxicity hampers pharmaceutical development. We designed and synthesized a derivative of RUT, bromo-dimethoxyrutaecarpine (Br-RUT, which showed no cytotoxicity at 20 μM. Br-RUT suppressed nitric oxide (NO production and tumor necrosis factor-α release in concentration-dependent (0~20 μM manners in lipopolysaccharide (LPS-treated RAW 264.7 macrophages; protein levels of inducible NO synthase (iNOS and cyclooxygenase-2 induced by LPS were downregulated. Br-RUT inhibited cell migration and invasion of ovarian carcinoma A2780 cells with 0~48 h of treatment. Furthermore, Br-RUT enhanced the expression of transient receptor potential vanilloid type 1 and activated endothelial NOS in human aortic endothelial cells. These results suggest that the synthetic Br-RUT possesses very low cytotoxicity but retains its activities against inflammation and vasodilation that could be beneficial for cardiovascular disease therapeutics.

Ecological and health risk-based characterization of agricultural soils contaminated with polycyclic aromatic hydrocarbons in the vicinity of a chemical plant in China.

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Liu, Geng; Niu, Junjie; Guo, Wenjiong; An, Xiangsheng; Zhao, Long

2016-11-01

Polycyclic aromatic hydrocarbons (PAHs) from chemical plants can cause serious pollution of surrounding agricultural soils. A comprehensive study of agricultural soils was conducted in the vicinity of a chemical plant in China to characterize the soil PAH concentration, as well as their composition and sources. Human health and a screening-level ecological risk assessment were conducted for PAH contamination in agricultural soils. The results showed that the total concentrations of 16 priority PAHs ranged from 250.49 to 9387.26 ng g(-1), with an average of 2780.42 ng g(-1). High molecular weight PAHs (four to six rings) were the dominant component, accounting for more than 60% of all PAHs. Principal component analysis (PCA) and positive matrix factorization model (PMF) suggested that diesel emissions, coal combustion, coke ovens, and fuel combustion and gasoline emissions were the main sources of PAHs in agricultural soils. The ecological risk assessment results based on the effects range-low (ERL), the effects range-median (ERM), and the ecological screening levels (ESL) indicated that the exposure to ∑PAH16 was >ERL, >ERM, and ≥ERL and ESL at 78.1% of the soil sampling stations, and could induce biological effects in mammals. The Bapeq concentrations posed a potential carcinogenic risk to humans. Further risk management and control of soil PAHs in these agricultural soils is required to ensure the safety of the biocoenosis and human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feasibility of the optical imaging of thrombus formation in a rotary blood pump by near-infrared light.

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Sakota, Daisuke; Murashige, Tomotaka; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu

2014-09-01

Blood coagulation is one of the primary concerns when using mechanical circulatory support devices such as blood pumps. Noninvasive detection and imaging of thrombus formation is useful not only for the development of more hemocompatible devices but also for the management of blood coagulation to avoid risk of infarction. The objective of this study is to investigate the use of near-infrared light for imaging of thrombus formation in a rotary blood pump. The optical properties of a thrombus at wavelengths ranging from 600 to 750 nm were analyzed using a hyperspectral imaging (HSI) system. A specially designed hydrodynamically levitated centrifugal blood pump with a visible bottom area was used. In vitro antithrombogenic testing was conducted five times with the pump using bovine whole blood in which the activated blood clotting time was adjusted to 200 s prior to the experiment. Two halogen lights were used for the light sources. The forward scattering through the pump and backward scattering on the pump bottom area were imaged using the HSI system. HSI showed an increase in forward scattering at wavelengths ranging from 670 to 750 nm in the location of thrombus formation. The time at which the thrombus began to form in the impeller rotating at 2780 rpm could be detected. The spectral difference between the whole blood and the thrombus was utilized to image thrombus formation. The results indicate the feasibility of dynamically detecting and imaging thrombus formation in a rotary blood pump. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Practical considerations on frenectomy

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Moldoveanu, Lucia; Badea, Florin Ciprian; Odor, Alin A.

2014-01-01

Besides surgically classical frenectomy, modern dentistry currently allows its approach by dental laser. Materials and Method: We proposed clinical observation of the results obtained by frenectomy with/without frenoplasty made by laser Er,Cr:YSGG 2780 nm. Results: The patients reported no pain, bleeding, swelling or major discomfort during the postoperative control of the following day. In terms of psycho-emotional reactions, both patients well behave well, the calm being given by no pain, bleeding, suture or edema. Discussions: The accuracy of this method, as well as the use of additional means of healing, allow satisfactory results both for patient and physician. Working parameters depend on the type of laser that is used, in our case Biolase Waterlase MD Turbo, regularly used in Toldimed Clinic in Constanta. Conclusions: Our study reveals that the possibilities regarding the surgical modeling of the lower lip frenulum are higher due to laser than the classical surgical approach. Moreover, a major role in the prevention of relapse by inappropriate healing is represented by the approach of frenectomy accompanied by frenuloplasty.

Re-Os ages for Archean molybdenite and pyrite, Kuittila-Kivisuo, Finland and Proterozoic molybdenite, Kabeliai, Lithuania: Testing the chronometer in a metamorphic and metasomatic setting

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Stein, H.J.; Sundblad, K.; Markey, R.J.; Morgan, J.W.; Motuza, G.

1998-01-01

that the Re-Os isotopic system in pyrite has been reset on the millimeter scale and that the 21 ppt 187Os intercept reflects the in situ decay of 187Re during the ~160 to 170 m.y. interval from ~2778 Ma (time of molybdenite ± pyrite deposition) to ~2607 Ma (time of pyrite resetting). When the Re-Os data for molybdenites from the nearby Kivisuo prospect are plotted together with the Kuittila molybdenite and pyrite data, a well-constrained five-point isochron with an age of 2780 ± 8 Ma and a 187Os intercept (-2.4 ± 3.8 ppt) of essentially zero results (MSWD = 1.5). We suggest that the pyrite isochron age records a regional metamorphic and/or hydrothermal event, possibly the time of Au mineralization. A proposed Re-Os age of ~2607 Ma for Au mineralization is in good agreement with radiometric ages by other methods that address the timing of Archean Au mineralization in deposits worldwide (so-called 'late Au model'). Molybdenite, in contrast, provides a robust Re-Os chronometer, retaining its original formation age of ~2780 Ma, despite subsequent metamorphic disturbances in Archean and Proterozoic time.

The Positive Outcome of MRI-Guided Vacuum Assisted Core Needle Breast Biopsies Is Not Influenced by a Prior Negative Targeted Second-Look Ultrasound.

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Ferré, Romuald; AlSharif, Shaza; Aldis, Ann; Mesurolle, Benoît

2017-11-01

The study sought to investigate the outcome of breast magnetic resonance-guided biopsies as a function of the indication for magnetic resonance imaging (MRI), the MRI features of the lesions, and the performance or not of a targeted second-look ultrasound (SLUS) prior breast MRI-guided biopsy. We identified 158 women with MRI-detected breast lesions scheduled for MRI-guided biopsy (2007-2013). Patient demographics, performance of targeted SLUS, imaging characteristics, and subsequent pathology results were reviewed. Three biopsies were deferred, and 155 lesions were biopsied under MRI guidance (155 women; median age 55.14 years; range 27-80 years). Ninety-eight women underwent a SLUS prior to the MRI-guided biopsy (63%). Of the 155 biopsied lesions, 23 (15%) were malignant, 106 (68%) were benign, and 26 (17%) were high risk. Four of 15 surgically excised high-risk lesions were upgraded to malignancy (27%). Most of the biopsied lesions corresponded to non-mass-like enhancement (81%, 126 of 155) and most of the biopsies (52%, 81 of 155) were performed in a screening context. No demographic or MRI features were associated with malignancy. No differences were noted between the 2 subgroups (prior SLUS vs no prior SLUS) except for the presence of a synchronous carcinoma associated with a likelihood of targeted SLUS before MRI-guided biopsy (P = .001). A negative SLUS does not influence the pathology outcome of a suspicious lesion biopsied under MR guidance. Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

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Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo Cheol; Yoon, Jung Hwan; Park, Jae Hyung; Chung, He Son

2009-01-01

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3- BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% ± 7.6 [mean ± SD]) than that in the control group (48% ± 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% ± 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% ± 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method

The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

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Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

Energy Technology Data Exchange (ETDEWEB)

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo Cheol; Yoon, Jung Hwan; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of); Chung, He Son [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2009-12-15

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3- BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +- 7.6 [mean +- SD]) than that in the control group (48% +- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method

Therapeutic effect of Chinese herbal medicines for post stroke recovery: A traditional and network meta-analysis.

Science.gov (United States)

Han, Shi-You; Hong, Zhi-You; Xie, Yu-Hua; Zhao, Yong; Xu, Xiao

2017-12-01

Stroke is a condition with high morbidity and mortality, and 75% of stroke survivors lose their ability to work. Stroke is a burden to the family and society. The purpose of this study was to evaluate the effectiveness of Chinese herbal patent medicines in the treatment of patients after the acute phase of a stroke. We searched the following databases through August 2016: PubMed, Embase, Cochrane library, China Knowledge Resource Integrated Database (CNKI), China Science Periodical Database (CSPD), and China Biology Medicine disc (CBMdisc) for studies that evaluated Chinese herbal patent medicines for post stroke recovery. A random-effect model was used to pool therapeutic effects of Chinese herbal patent medicines on stroke recovery. Network meta-analysis was used to rank the treatment for each Chinese herbal patent medicine. In our meta-analysis, we evaluated 28 trials that included 2780 patients. Chinese herbal patent medicines were effective in promoting recovery after stroke (OR, 3.03; 95% CI: 2.53-3.64; P herbal patent medicines significantly improved neurological function defect scores when compared with the controls (standard mean difference [SMD], -0.89; 95% CI, -1.44 to -0.35; P = .001). Chinese herbal patent medicines significantly improved the Barthel index (SMD, 0.73; 95% CI, 0.53-0.94; P herbal medicines most likely to improve stroke recovery when combined with acupuncture. Our research suggests that the Chinese herbal patent medicines were effective for stroke recovery. The most effective treatments for stroke recovery were MLC601, Shuxuetong, and BuchangNaoxintong. However, to clarify the specific effective ingredients of Chinese herbal medicines, a well-designed study is warranted.

Associação entre violência por parceiro íntimo contra a mulher e infecção por HIV Asociación entre violencia contra la mujer por pareja íntima e infección por VIH Association between intimate partner violence against women and HIV infection

Directory of Open Access Journals (Sweden)

Claudia Barros

2011-04-01

Full Text Available OBJETIVO: Analisar a associação entre a violência por parceiro íntimo contra mulheres e a infecção ou suspeita de infecção pelo vírus da imunodeficiência humana (HIV. MÉTODOS: Estudo transversal com base em dados de questionários aplicados face-a-face e de prontuários médicos de 2.780 mulheres de 15 a 49 anos, atendidas em unidades do sistema único de saúde da Grande São Paulo, SP, em 2001-2002. As mulheres foram categorizadas em: usuárias em tratamento por serem "soropositivas para o HIV", com "suspeita de HIV" e aquelas que procuraram os serviços por outros motivos. A violência por parceiro íntimo contra mulheres na vida foi categorizada por gravidade e recorrência dos episódios de violência. A associação com o desfecho foi testada pelo modelo de Poisson com variância robusta e ajustada por variáveis sociodemográficas, sexuais e reprodutivas. RESULTADOS: A prevalência de violência foi de 59,8%. Sofrer violência reiterada e grave apresentou maior associação de infecção confirmada pelo HIV (RP = 1,91. A violência independente da gravidade e da recorrência dos episódios apresentou maior associação para a suspeita de infecção por HIV (RP = 1,29. CONCLUSÕES: A violência por parceiro íntimo contra mulheres tem papel relevante nas situações de suspeita e confirmação da infecção pelo HIV, sendo essencial incluir sua detecção, controle e prevenção como parte da atenção integral à saúde das mulheres.OBJETIVO: Analizar la asociación entre la violencia contra mujeres por pareja íntima y la infección o sospecha de infección por el virus de inmunodeficiencia humana (VIH. MÉTODOS: Estudio transversal con base en datos de cuestionarios aplicados cara-a cara y de prontuarios médicos de 2.780 mujeres de 15 a 49 años, atendidas en unidades del sistema único de salud de la Gran Sao Paulo, Sureste de Brasil, en 2001-2002. Las mujeres fueron categorizadas en: usuarias en tratamiento por ser

vPARP Adjusts MVP Expression in Drug-resistant Cell Lines in Conjunction with MDR Proteins.

Science.gov (United States)

Wojtowicz, Karolina; Januchowski, Radoslaw; Nowicki, Michal; Zabel, Maciej

2017-06-01

The definition of vault (ribonucleoprotein particles) function remains highly complex. Vaults may cooperate with multidrug resistance (MDR) proteins, supporting their role in drug resistance. This topic is the main theme of this publication. The cell viability was determined by an MTT assay. The protein expression was detected by western blot analysis. The proteins were knocked-down using siRNA. No major vault protein (MVP) in the LoVo/Dx and W1PR cell lines after tunicamycin treatment was shown. In W1PR cells with knocked-down MVP, a statistically significant decrease in cell viability was noted. In LoVo/Dx, W1TR and A2780TR cells were vault poly-ADP-ribose polymerase (vPARP) was knockdown, a decrease in cell viability was shown. Also, MVP silencing induced an increase in glycoprotein P (Pgp) expression in LoVo/Dx cells. MVP is important for the drug resistance of cancer cells, but it probably requires the presence of vPARP for full activation. Some correlations between MDR proteins and vaults exist. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Poly(amido)amine (PAMAM) dendrimer–cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

International Nuclear Information System (INIS)

Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

2013-01-01

Dendrimer–cisplatin complexes were prepared using PAMAM dendrimers with terminal –NH 2 and –COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer–cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was ∼11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC 50 values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum–DNA adduct formation. Treatment with dendrimer–cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

Energy Technology Data Exchange (ETDEWEB)

Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath, E-mail: palakurthi@tamhsc.edu [Texas A and M Health Science Center, Irma Lerma Rangel College of Pharmacy (United States)

2013-09-15

Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH{sub 2} and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was {approx}11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC{sub 50} values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

Fine mapping of the sunflower resistance locus PlARG introduced from the wild species Helianthus argophyllus

Science.gov (United States)

Wieckhorst, S.; Bachlava, E.; Dußle, C. M.; Tang, S.; Gao, W.; Saski, C.; Knapp, S. J.; Schön, C.-C.; Hahn, V.

2010-01-01

Downy mildew, caused by Plasmopara halstedii, is one of the most destructive diseases in cultivated sunflower (Helianthus annuus L.). The dominant resistance locus PlARG originates from silverleaf sunflower (H. argophyllus Torrey and Gray) and confers resistance to all known races of P. halstedii. We mapped PlARG on linkage group (LG) 1 of (cms)HA342 × ARG1575-2, a population consisting of 2,145 F2 individuals. Further, we identified resistance gene candidates (RGCs) that cosegregated with PlARG as well as closely linked flanking markers. Markers from the target region were mapped with higher resolution in NDBLOSsel × KWS04, a population consisting of 2,780 F2 individuals that does not segregate for PlARG. A large-insert sunflower bacterial artificial chromosome (BAC) library was screened with overgo probes designed for markers RGC52 and RGC151, which cosegregated with PlARG. Two RGC-containing BAC contigs were anchored to the PlARG region on LG 1. Electronic supplementary material The online version of this article (doi:10.1007/s00122-010-1416-4) contains supplementary material, which is available to authorized users. PMID:20700574

Total phenolics and antioxidant activity of five medicinal plant

International Nuclear Information System (INIS)

Sousa, Cleyton Marcos de M.; Silva, Hilris Rocha e; Vieira-Junior, Gerardo Magela; Ayres, Mariane Cruz C.; Costa, Charllyton Luis S. da; Araajo, Delton Servulo; Cavalcante, Luis Carlos D.; Barros, Elcio Daniel S.; Araujo, Paulo Breitner de M.; Brandao, Marcela S.; Chaves, Mariana H.

2007-01-01

This paper describes total phenolics content and antioxidant activity in the ethanolic extract of leaves, bark and roots of five medicinal plants: Terminalia brasiliensis Camb., Terminalia fagifolia Mart. and Zucc., Copernicia cerifera (Miller) H.E. Moore, Cenostigma macrophyllum Tul. var. acuminata Teles Freire and Qualea grandiflora Mart. The total phenolics content of the plant extracts, determined by the Folin-Ciocalteu method, varied from 250.0 ±8,2 to 763,63 ±13.03 mg of gallic acid equivalent/g dry EtOH extract. The antioxidant activity of extracts was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay system. Extract of bark from T. brasiliensis, the most active, with an EC 50 value of 27.59 ± 0.82 μg/mL, was comparable to rutin (EC 50 = 27.80 ± 1.38) and gallic acid (EC 50 = 24.27 ± 0.31), used as positive controls. The relationship between total phenolic content and antioxidant activity was positive and significant for T. brasiliensis, C. macrophyllum and C. cerifera. (author)

Total phenolics and antioxidant activity of five medicinal plant; Fenois totais e atividade antioxidante de cinco plantas medicinais

Energy Technology Data Exchange (ETDEWEB)

Sousa, Cleyton Marcos de M.; Silva, Hilris Rocha e; Vieira-Junior, Gerardo Magela; Ayres, Mariane Cruz C.; Costa, Charllyton Luis S. da; Araajo, Delton Servulo; Cavalcante, Luis Carlos D.; Barros, Elcio Daniel S.; Araujo, Paulo Breitner de M.; Brandao, Marcela S.; Chaves, Mariana H. [Universidade Federal do Piaui, Teresina, PI (Brazil). Dept. de Quimica]. E-mail: mariana@ufpi.br

2007-03-15

This paper describes total phenolics content and antioxidant activity in the ethanolic extract of leaves, bark and roots of five medicinal plants: Terminalia brasiliensis Camb., Terminalia fagifolia Mart. and Zucc., Copernicia cerifera (Miller) H.E. Moore, Cenostigma macrophyllum Tul. var. acuminata Teles Freire and Qualea grandiflora Mart. The total phenolics content of the plant extracts, determined by the Folin-Ciocalteu method, varied from 250.0 {+-}8,2 to 763,63 {+-}13.03 mg of gallic acid equivalent/g dry EtOH extract. The antioxidant activity of extracts was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay system. Extract of bark from T. brasiliensis, the most active, with an EC{sub 50} value of 27.59 {+-} 0.82 {mu}g/mL, was comparable to rutin (EC{sub 50} = 27.80 {+-} 1.38) and gallic acid (EC{sub 50} = 24.27 {+-} 0.31), used as positive controls. The relationship between total phenolic content and antioxidant activity was positive and significant for T. brasiliensis, C. macrophyllum and C. cerifera. (author)

Interaction between doubly-excited 4p4nln'l' resonances in KrI

International Nuclear Information System (INIS)

Sukhorukov, V L; Petrov, I D; Demekhin, Ph V; Schmoranzer, H; Mickat, S; Kammer, S; Schartner, K-H; Klumpp, S; Werner, L; Ehresmann, A

2007-01-01

Photoionization cross sections for the 4p 4 ( 3 P)5s 4 P 5/2,3/2,1/2 satellites and 4s → εl, 4p → εl main lines of Kr II were measured using the photon-induced fluorescence spectroscopy in the exciting-photon energy range between 27.80 eV and 29.44 eV with extremely narrow bandwidth (1.7 meV at 28.55 eV) of the monochromatized synchrotron radiation. The observed resonances were assigned to the 4p 4 5s( 4 P 1/2 )np and 4p 4 5s( 2 P 3/2 )np Rydberg series on the basis of the calculations including core relaxation and interaction between many resonances and many continua. The calculation shows that the resonance structure in the photoionization channels exists due to the 4p 4 ( 1 D)5s 2 D 5/2 6p 3/2 and 4p 4 ( 1 D)5s 2 D 3/2 6p 3/2,1/2 promoter states which strongly perturb the above Rydberg series

Crystal Structure of Mycobacterium tuberculosis H37Rv AldR (Rv2779c), a Regulator of the ald Gene: DNA BINDING AND IDENTIFICATION OF SMALL MOLECULE INHIBITORS.

Science.gov (United States)

Dey, Abhishek; Shree, Sonal; Pandey, Sarvesh Kumar; Tripathi, Rama Pati; Ramachandran, Ravishankar

2016-06-03

Here we report the crystal structure of M. tuberculosis AldR (Rv2779c) showing that the N-terminal DNA-binding domains are swapped, forming a dimer, and four dimers are assembled into an octamer through crystal symmetry. The C-terminal domain is involved in oligomeric interactions that stabilize the oligomer, and it contains the effector-binding sites. The latter sites are 30-60% larger compared with homologs like MtbFFRP (Rv3291c) and can consequently accommodate larger molecules. MtbAldR binds to the region upstream to the ald gene that is highly up-regulated in nutrient-starved tuberculosis models and codes for l-alanine dehydrogenase (MtbAld; Rv2780). Further, the MtbAldR-DNA complex is inhibited upon binding of Ala, Tyr, Trp and Asp to the protein. Studies involving a ligand-binding site G131T mutant show that the mutant forms a DNA complex that cannot be inhibited by adding the amino acids. Comparative studies suggest that binding of the amino acids changes the relative spatial disposition of the DNA-binding domains and thereby disrupt the protein-DNA complex. Finally, we identified small molecules, including a tetrahydroquinoline carbonitrile derivative (S010-0261), that inhibit the MtbAldR-DNA complex. The latter molecules represent the very first inhibitors of a feast/famine regulatory protein from any source and set the stage for exploring MtbAldR as a potential anti-tuberculosis target. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer

International Nuclear Information System (INIS)

Hijaz, Miriana; Das, Soumen; Mert, Ismail; Gupta, Ankur; Al-Wahab, Zaid; Tebbe, Calvin; Dar, Sajad; Chhina, Jasdeep; Giri, Shailendra; Munkarah, Adnan; Seal, Sudipta; Rattan, Ramandeep

2016-01-01

Nanomedicine is a very promising field and nanomedical drugs have recently been used as therapeutic agents against cancer. In a previous study, we showed that Nanoceria (NCe), nanoparticles of cerium oxide, significantly inhibited production of reactive oxygen species, cell migration and invasion of ovarian cancer cells in vitro, without affecting cell proliferation and significantly reduced tumor growth in an ovarian cancer xenograft nude model. Increased expression of folate receptor-α, an isoform of membrane-bound folate receptors, has been described in ovarian cancer. To enable NCe to specifically target ovarian cancer cells, we conjugated nanoceria to folic acid (NCe-FA). Our aim was to investigate the pre-clinical efficacy of NCe-FA alone and in combination with Cisplatin. Ovarian cancer cell lines were treated with NCe or NCe-FA. Cell viability was assessed by MTT and colony forming units. In vivo studies were carried in A2780 generated mouse xenografts treated with 0.1 mg/Kg NCe, 0.1 mg/Kg; NCe-FA and cisplatinum, 4 mg/Kg by intra-peritoneal injections. Tumor weights and burden scores were determined. Immunohistochemistry and toxicity assays were used to evaluate treatment effects. We show that folic acid conjugation of NCe increased the cellular NCe internalization and inhibited cell proliferation. Mice treated with NCe-FA had a lower tumor burden compared to NCe, without any vital organ toxicity. Combination of NCe-FA with cisplatinum decreased the tumor burden more significantly. Moreover, NCe-FA was also effective in reducing proliferation and angiogenesis in the xenograft mouse model. Thus, specific targeting of ovarian cancer cells by NCe-FA holds great potential as an effective therapeutic alone or in combination with standard chemotherapy. The online version of this article (doi:10.1186/s12885-016-2206-4) contains supplementary material, which is available to authorized users

Graphene Oxide–Silver Nanocomposite Enhances Cytotoxic and Apoptotic Potential of Salinomycin in Human Ovarian Cancer Stem Cells (OvCSCs: A Novel Approach for Cancer Therapy

Directory of Open Access Journals (Sweden)

Yun-Jung Choi

2018-03-01

Full Text Available The use of graphene to target and eliminate cancer stem cells (CSCs is an alternative approach to conventional chemotherapy. We show the biomolecule-mediated synthesis of reduced graphene oxide–silver nanoparticle nanocomposites (rGO–Ag using R-phycoerythrin (RPE; the resulting RPE–rGO–Ag was evaluated in human ovarian cancer cells and ovarian cancer stem cells (OvCSCs. The synthesized RPE–rGO–Ag nanocomposite (referred to as rGO–Ag was characterized using various analytical techniques. rGO–Ag showed significant toxicity towards both ovarian cancer cells and OvCSCs. After 3 weeks of incubating OvCSCs with rGO–Ag, the number of A2780 and ALDH+CD133+ colonies was significantly reduced. rGO–Ag was toxic to OvCSCs and reduced cell viability by mediating the generation of reactive oxygen species, leakage of lactate dehydrogenase, reduced mitochondrial membrane potential, and enhanced expression of apoptotic genes, leading to mitochondrial dysfunction and possibly triggering apoptosis. rGO–Ag showed significant cytotoxic potential towards highly tumorigenic ALDH+CD133+ cells. The combination of rGO–Ag and salinomycin induced 5-fold higher levels of apoptosis than each treatment alone. A combination of rGO–Ag and salinomycin at very low concentrations may be suitable for selectively killing OvCSCs and sensitizing tumor cells. rGO–Ag may be a novel nano-therapeutic molecule for specific targeting of highly tumorigenic ALDH+CD133+ cells and eliminating CSCs. This study highlights the potential for targeted therapy of tumor-initiating cells.

Spatial and temporal corroboration of a fire-scar-based fire history in a frequently burned ponderosa pine forest.

Science.gov (United States)

Farris, Calvin A; Baisan, Christopher H; Falk, Donald A; Yool, Stephen R; Swetnam, Thomas W

2010-09-01

Fire scars are used widely to reconstruct historical fire regime parameters in forests around the world. Because fire scars provide incomplete records of past fire occurrence at discrete points in space, inferences must be made to reconstruct fire frequency and extent across landscapes using spatial networks of fire-scar samples. Assessing the relative accuracy of fire-scar fire history reconstructions has been hampered due to a lack of empirical comparisons with independent fire history data sources. We carried out such a comparison in a 2780-ha ponderosa pine forest on Mica Mountain in southern Arizona (USA) for the time period 1937-2000. Using documentary records of fire perimeter maps and ignition locations, we compared reconstructions of key spatial and temporal fire regime parameters developed from documentary fire maps and independently collected fire-scar data (n = 60 plots). We found that fire-scar data provided spatially representative and complete inventories of all major fire years (> 100 ha) in the study area but failed to detect most small fires. There was a strong linear relationship between the percentage of samples recording fire scars in a given year (i.e., fire-scar synchrony) and total area burned for that year (y = 0.0003x + 0.0087, r2 = 0.96). There was also strong spatial coherence between cumulative fire frequency maps interpolated from fire-scar data and ground-mapped fire perimeters. Widely reported fire frequency summary statistics varied little between fire history data sets: fire-scar natural fire rotations (NFR) differed by or = 25% of study area burned) were identical between data sets (25.5 yr); fire-scar MFIs for all fire years differed by 1.2 yr from documentary records. The known seasonal timing of past fires based on documentary records was furthermore reconstructed accurately by observing intra-annual ring position of fire scars and using knowledge of tree-ring growth phenology in the Southwest. Our results demonstrate clearly

Grazing alters net ecosystem C fluxes and the global warming potential of a subtropical pasture.

Science.gov (United States)

Gomez-Casanovas, Nuria; DeLucia, Nicholas J; Bernacchi, Carl J; Boughton, Elizabeth H; Sparks, Jed P; Chamberlain, Samuel D; DeLucia, Evan H

2018-03-01

The impact of grazing on C fluxes from pastures in subtropical and tropical regions and on the environment is uncertain, although these systems account for a substantial portion of global C storage. We investigated how cattle grazing influences net ecosystem CO 2 and CH 4 exchange in subtropical pastures using the eddy covariance technique. Measurements were made over several wet-dry seasonal cycles in a grazed pasture, and in an adjacent pasture during the first three years of grazer exclusion. Grazing increased soil wetness but did not affect soil temperature. By removing aboveground biomass, grazing decreased ecosystem respiration (R eco ) and gross primary productivity (GPP). As the decrease in R eco was larger than the reduction in GPP, grazing consistently increased the net CO 2 sink strength of subtropical pastures (55, 219 and 187 more C/m 2 in 2013, 2014, and 2015). Enteric ruminant fermentation and increased soil wetness due to grazers, increased total net ecosystem CH 4 emissions in grazed relative to ungrazed pasture (27-80%). Unlike temperate, arid, and semiarid pastures, where differences in CH 4 emissions between grazed and ungrazed pastures are mainly driven by enteric ruminant fermentation, our results showed that the effect of grazing on soil CH 4 emissions can be greater than CH 4 produced by cattle. Thus, our results suggest that the interactions between grazers and soil hydrology affecting soil CH 4 emissions play an important role in determining the environmental impacts of this management practice in a subtropical pasture. Although grazing increased total net ecosystem CH 4 emissions and removed aboveground biomass, it increased the net storage of C and decreased the global warming potential associated with C fluxes of pasture by increasing its net CO 2 sink strength. © 2017 by the Ecological Society of America.

Productino of KSR-III Airglow Photometers to Measure MUV Airglows of the Upper Atmosphere Above the Korean Peninsular

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T. H. Oh

2002-12-01

Full Text Available We have constructed two flight models of airglow photometer system (AGP to be onboard Korea Sounding Rocket-III (KSR-III for detection of MUV dayglow above the Korean peninsular. The AGP system is designed to detect dayglow emissions of OI 2972 Å, N_2 VK (0,6 2780Å, N_2 2PG 3150Å and background 3070Å toward the horizon at altitudes between 100 km and 300 km. The AGP system consists of a photometer body, a baffle, an electronic control unit and a battery unit. The MUV dayglow emissions enter through a narrow band interference filter and focusing lens of the photometer, which contains an ultraviolet sensitive photomultiplier tube. The photometer is equipped with an in-flight calibration light source on a circular plane that will rotate at the rocket's apogee. A baffle tube is installed at the entry of the photometer in order to block strong scattering lights from the lower atmosphere. We have carried out laboratory measurements of sensitivity and in-flight calibration light source for the AGP flight models. Although absolute sensitivities of the AGP flight models could not be determined in the country, relative sensitivities among channels are well measured so that observation data during rocket flight in the future can be analyzed with confidence.

Cobalt nanoparticles for biomedical applications: Facile synthesis, physiochemical characterization, cytotoxicity behavior and biocompatibility

Science.gov (United States)

Ansari, S. M.; Bhor, R. D.; Pai, K. R.; Sen, D.; Mazumder, S.; Ghosh, Kartik; Kolekar, Y. D.; Ramana, C. V.

2017-08-01

Cobalt (Co) nanoparticles (NPs) were produced by a simple, one step hydrothermal method with the capping of oleic acid. Intrinsic structural, physiochemical and magnetic properties of Co NPs were investigated and demonstrated their applicability in biomedicine. X-ray diffraction, Raman spectroscopy and infrared (IR) spectroscopic studies confirm the single phase Co NPs with a high structural quality. The IR data revealed the capping of oleic acid via monodentate interaction. Small angle scattering studies suggest the existence of sticky hard sphere type of interaction among the Co NPs because of magnetic interaction which is further evidenced by electron microscopy imaging analyses. The Co NPs exhibit a ferromagnetic character over a wide range of temperature (20-300 K). The temperature dependence of magnetic parameters namely, saturation magnetization, remanent magnetization, coercivity and reduced remanent magnetization were determined and correlated with structure of Co NPs. The Cytotoxicity studies demonstrate that these Co NPs exhibit the mild anti-proliferative character against the cancer cells (cisplatin resistant ovarian cancer (A2780/CP70)) and safe nature towards the normal cells. Haemolytic behavior of human red blood cells (RBC) revealed (<5%) haemolysis signifying the compatibility of Co NPs with human RBC which is an essential feature in vivo biomedical applications without creating any harmful effects in the human blood stream.

Cobalt nanoparticles for biomedical applications: Facile synthesis, physiochemical characterization, cytotoxicity behavior and biocompatibility

Energy Technology Data Exchange (ETDEWEB)

Ansari, S.M. [Department of Physics, Savitribai Phule Pune University, Pune, 411007, Maharashtra (India); Bhor, R.D.; Pai, K.R. [Department of Zoology, Savitribai Phule Pune University, Pune, 411007, Maharashtra (India); Sen, D.; Mazumder, S. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai, 400 085 (India); Ghosh, Kartik [Department of Physics, Astronomy and Materials Science, Missouri State University, Springfield, MO, 65897 (United States); Kolekar, Y.D., E-mail: ydkolekar@gmail.com [Department of Physics, Savitribai Phule Pune University, Pune, 411007, Maharashtra (India); Ramana, C.V., E-mail: rvchintalapalle@utep.edu [Department of Mechanical Engineering, University of Texas at El Paso, El Paso, TX, 79968 (United States)

2017-08-31

Cobalt (Co) nanoparticles (NPs) were produced by a simple, one step hydrothermal method with the capping of oleic acid. Intrinsic structural, physiochemical and magnetic properties of Co NPs were investigated and demonstrated their applicability in biomedicine. X-ray diffraction, Raman spectroscopy and infrared (IR) spectroscopic studies confirm the single phase Co NPs with a high structural quality. The IR data revealed the capping of oleic acid via monodentate interaction. Small angle scattering studies suggest the existence of sticky hard sphere type of interaction among the Co NPs because of magnetic interaction which is further evidenced by electron microscopy imaging analyses. The Co NPs exhibit a ferromagnetic character over a wide range of temperature (20–300 K). The temperature dependence of magnetic parameters namely, saturation magnetization, remanent magnetization, coercivity and reduced remanent magnetization were determined and correlated with structure of Co NPs. The Cytotoxicity studies demonstrate that these Co NPs exhibit the mild anti-proliferative character against the cancer cells (cisplatin resistant ovarian cancer (A2780/CP70)) and safe nature towards the normal cells. Haemolytic behavior of human red blood cells (RBC) revealed (<5%) haemolysis signifying the compatibility of Co NPs with human RBC which is an essential feature in vivo biomedical applications without creating any harmful effects in the human blood stream.

Dietary intake, food processing, and cooking methods among Amish and non-Amish adults living in Ohio Appalachia: relevance to nutritional risk factors for cancer.

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Cuyun Carter, Gebra B; Katz, Mira L; Ferketich, Amy K; Clinton, Steven K; Grainger, Elizabeth M; Paskett, Electra D; Bloomfield, Clara D

2011-11-01

This study's purpose was to examine the source, storage, preparation, and intake of food among Amish and non-Amish adults to understand dietary practices as a potential contributing factor to lower cancer incidence rates. Interviews were conducted with a random sample of 134 Amish and 154 non-Amish adults including questions about dietary practices and a 24-h dietary recall. Amish compared to non-Amish adults reported (1) less refrigeration in homes (85% vs. 100%, P alcohol (P < .01); (4) consuming fewer daily servings of vegetables (males: 1.2 vs. 1.9 servings/day, P < .01; females: 1.0 vs. 2.1 servings/day, P < .01); and (5) a greater percentage of energy from saturated fat (males: 16.7% vs. 12.6%, P < .01; females: 16.3% vs. 12.0%, P < .01). Amish males reported greater amount of energy intake (2780 kcal vs. 2298 kcal, P = .03) compared to non-Amish males. Amish and non-Amish dietary patterns show some differences that may impact cancer although neither group achieves current diet and cancer prevention guidelines. Lifestyle factors, screening, and healthcare access may be contributing to the lower cancer incidence rates among the Amish and these results suggest areas of intervention to reduce the cancer burden.

Associação entre violência por parceiro íntimo contra a mulher e infecção por HIV

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Claudia Barros

2011-04-01

Full Text Available OBJETIVO: Analisar a associação entre a violência por parceiro íntimo contra mulheres e a infecção ou suspeita de infecção pelo vírus da imunodeficiência humana (HIV. MÉTODOS: Estudo transversal com base em dados de questionários aplicados face-a-face e de prontuários médicos de 2.780 mulheres de 15 a 49 anos, atendidas em unidades do sistema único de saúde da Grande São Paulo, SP, em 2001-2002. As mulheres foram categorizadas em: usuárias em tratamento por serem "soropositivas para o HIV", com "suspeita de HIV" e aquelas que procuraram os serviços por outros motivos. A violência por parceiro íntimo contra mulheres na vida foi categorizada por gravidade e recorrência dos episódios de violência. A associação com o desfecho foi testada pelo modelo de Poisson com variância robusta e ajustada por variáveis sociodemográficas, sexuais e reprodutivas. RESULTADOS: A prevalência de violência foi de 59,8%. Sofrer violência reiterada e grave apresentou maior associação de infecção confirmada pelo HIV (RP = 1,91. A violência independente da gravidade e da recorrência dos episódios apresentou maior associação para a suspeita de infecção por HIV (RP = 1,29. CONCLUSÕES: A violência por parceiro íntimo contra mulheres tem papel relevante nas situações de suspeita e confirmação da infecção pelo HIV, sendo essencial incluir sua detecção, controle e prevenção como parte da atenção integral à saúde das mulheres.

Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

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Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

2005-11-15

One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

Clinical and MRI features of prostate sarcoma: comparison with prostate adenocarcinoma

International Nuclear Information System (INIS)

Ding Jianping; Wang Xiaoying; Wang Zhenzhong; Zhou Liangping; Jiang Xuexiang

2004-01-01

Objective: To summarize the clinical and imaging features of prostate sarcoma, and to compare the features with those of prostate adenocarcinoma (PCa). Method: Six cases of prostate sarcoma proved pathologically were enrolled in this study. The clinical material and imaging features were compared with those of the PCa. Results: (1) Pathological result: Among the 6 prostate sarcomas, 3 were rhabdomyosarcoma, 1 was leiomyosarcoma, and 2 were sarcoma originated from interstitial tissue that could not be classified. (2) Clinical result: The 6 patients of sarcoma were younger (median age 36.5, 15-71 years) than the patients of PCa (median age 72, 50-78 years) (P -3 ng/L] was normal and lower than that of the PCa patients [median 27.80, (1.55-352.00) x 10 -3 ng/ L] (P 3 ) was larger than that of PCa (median 41.57, 17.16-179.44 cm 3 ) (P 2 -weighted images, with grossly normal structure of the prostate. Excapsular extension was more common in the sarcomas than in the PCa (83.3% vs 66.7%). Conclusion: The clinical and imaging features of prostate sarcoma are different from those of prostate adenocarcinoma

Determination of free cisplatin in medium by differential pulse polarography after ultrasound and cisplatin treatment of a cancer cell culture

International Nuclear Information System (INIS)

Bernard, Vladan; Skorpikova, Jirina; Mornstein, Vojtech; Fojt, Lukas

2011-01-01

The in vitro study was carried out for detection of the cisplatin in free form and in culture medium, depending on various conditions of sonodynamic human ovarian cancer cells A2780 treatment by differential pulse polarography (DPP). For sonodynamic treatment, we used cisplatin alone and combined cisplatin/ultrasound treatments. The ultrasound exposure intensity of 1.0 and 2.0 Wcm 2 in far field for incubation periods 1, 24 and 48 h was used. The parameters of DPP measurements were - 1 s drop time, 5 mV.s -1 voltage scan rate, 50 mV modulation amplitude and negative scanning direction; platinum wire served as counter electrode and Ag|AgCl|3 M KCI as reference electrode. The results showed the dependence of free platinum quantities in culture medium on incubation time and treatment protocol. We found difference in concentration of free cisplatin between conventional application of cisplatin and sonodynamic treatment. The sonodynamic combined treatment of cisplatin and ultrasound field showed a higher cisplatin content in the culture medium than cisplatin treatment alone; a difference of 20% was observed for incubation time 48 h. The results also showed the influence of a time sequence of ultrasound and cytostatics in the sonodynamic treatment. The highest amount of free cisplatin in the solution was found for primary application of cisplatin and the subsequent ultrasound exposure. The quantity of free cisplatin increased with time, namely for time intervals 1-24 h. There was no difference between the DPP signal of cisplatin in reaction mixture containing cells in small quantities and micro-filtered mixture without cells. Thus, the DPP method is suitable for the detection and quantification of free cisplatin in the culture medium of cell suspension. Ultrasound field can be important factor during cytostatic therapy. (author)

Expected lifetime numbers, risks, and burden of osteoporotic fractures for 50-year old Chinese women: a discrete event simulation incorporating FRAX.

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Jiang, Yawen; Ni, Weiyi

2016-11-01

This work was undertaken to provide an estimation of expected lifetime numbers, risks, and burden of fractures for 50-year-old Chinese women. A discrete event simulation model was developed to simulate the lifetime fractures of 50-year-old Chinese women at average risk of osteoporotic fracture. Main events in the model included hip fracture, clinical vertebral fracture, wrist fracture, humerus fracture, and other fracture. Fracture risks were calculated using the FRAX ® tool. Simulations of 50-year-old Chinese women without fracture risks were also carried out as a comparison to determine the burden of fractures. A 50-year-old Chinese woman at average risk of fracture is expected to experience 0.135 (95 % CI: 0.134-0.137) hip fractures, 0.120 (95 % CI: 0.119-0.122) clinical vertebral fractures, 0.095 (95 % CI: 0.094-0.096) wrist fractures, 0.079 (95 % CI: 0.078-0.080) humerus fractures, and 0.407 (95 % CI: 0.404-0.410) other fractures over the remainder of her life. The residual lifetime risk of any fracture, hip fracture, clinical vertebral fracture, wrist fracture, humerus fracture, and other fracture for a 50-year-old Chinese woman is 37.36, 11.77, 10.47, 8.61, 7.30, and 27.80 %, respectively. The fracture-attributable excess quality-adjusted life year (QALY) loss and lifetime costs are estimated at 0.11 QALYs (95 % CI: 0.00-0.22 QALYs) and US $714.61 (95 % CI: US $709.20-720.02), totaling a net monetary benefit loss of US $1,104.43 (95 % CI: US $904.09-1,304.78). Chinese women 50 years of age are at high risk of osteoporotic fracture, and the expected economic and quality-of-life burden attributable to osteoporotic fractures among Chinese women is substantial.

Molecular survey of Bartonella henselae and Bartonella clarridgeiae in pet cats across Japan by species-specific nested-PCR.

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Sato, S; Kabeya, H; Negishi, A; Tsujimoto, H; Nishigaki, K; Endo, Y; Maruyama, S

2017-10-01

Cats are known to be the main reservoir for Bartonella henselae and Bartonella clarridgeiae, which are the agents of 'cat-scratch disease' in humans. In the present study, we investigated the prevalence of the two Bartonella species on 1754 cat bloods collected from all prefectures in Japan during 2007-2008 by a nested-polymerase chain reaction (PCR) targeting the 16S-23S rRNA internal transcribed spacer region. Overall, Bartonella DNA was detected in 4·6% (80/1754) of the cats examined. The nested-PCR showed that 48·8% (39/80) of the positive cats were infected with B. henselae mono-infection, 33·8% (27/80) with B. clarridgeiae mono-infection and 17·5% (14/80) were infected with both species. The prevalence (5·9%; 65/1103) of Bartonella infection in the western part of Japan was significantly higher than that (2·3%; 15/651) of eastern Japan (P < 0·001). Statistical analysis of the cats examined suggested a significant association between Bartonella infection and FeLV infection (OR = 1·9; 95% CI = 1·1-3·4), but not with FIV infection (OR = 1·6; 95% CI = 1·0-2·6).

Decreased stability of DNA in cells treated with alkylating agents

Energy Technology Data Exchange (ETDEWEB)

Frankfurt, O.S. (Cedars Medical Center, Miami, FL (United States))

1990-12-01

A modified highly sensitive procedure for the evaluation of DNA damage in individual cells treated with alkylating agents is reported. The new methodology is based on the amplification of single-strandedness in alkylated DNA by heating in the presence of Mg{sup 2+}. Human ovarian carcinoma cells A2780 were treated with nitrogen mustard (HN2), fixed in methanol, and stained with monoclonal antibody (MOAB) F7-26 generated against HN2-treated DNA. Binding of MOAB was measured by flow cytometry with indirect immunofluorescence. Intensive binding of MOAB to control and drug-treated cells was observed after heating in Tris buffer supplemented with MgCl{sub 2}. Thus, the presence of phosphates and MgCl{sub 2} during heating was necessary for the detection of HN2-induced changes in DNA stability. Fluorescence of HN2-treated cells decreased to background levels after treatment with single-strand-specific S{sub 1} nuclease. MOAB F7-26 interacted with single-stranded regions in DNA and did not bind to dsDNA or other cellular antigens. It is suggested that alkylation of guanines decreased the stability of the DNA molecule and increased the access of MOAB F7-26 to deoxycytidines on the opposite DNA strand.

New Abietane and Kaurane Type Diterpenoids from the Stems of Tripterygium regelii

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Dongsheng Fan

2017-01-01

Full Text Available Eleven new abietane type (1‒11, and one new kaurane (12, diterpenes, together with eleven known compounds (13–23, were isolated and identified from the stems of Tripterygium regelii, which has been used as a traditional folk Chinese medicine for the treatment of rheumatoid arthritis in China. The structures of new compounds were characterized by means of the interpretation of high-resolution electrospray ionization mass spectrometry (HRESIMS, extensive nuclear magnetic resonance (NMR spectroscopic data and comparisons of their experimental CD spectra with calculated electronic circular dichroism (ECD spectra. Compound 1 is the first abietane type diterpene with an 18→1 lactone ring. Compound 19 was isolated from the plants of the Tripterygium genus for the first time, and compounds 14–17 were isolated from T. regelii for the first time. Triregelin I (9 showed significant cytotoxicity against A2780 and HepG2 with IC50 values of 5.88 and 11.74 µM, respectively. It was found that this compound was inactive against MCF-7 cells. The discovery of these twelve new diterpenes not only provided information on chemical substances of T. regelii, but also contributed to the chemical diversity of natural terpenoids.

Study of in vitro antimicrobial and antiproliferative activities of selected Saharan plants.

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Palici, Ionut F; Liktor-Busa, Erika; Zupkó, István; Touzard, Blaise; Chaieb, Mohamed; Urbán, Edit; Hohmann, Judit

2015-12-01

The aim of the present study was the evaluation of the antimicrobial and antiproliferative activities of selected Saharan species, which are applied in the traditional medicine but not studied thoroughly from chemical and pharmacological point of view. The studied plants, namely Anthyllis henoniana, Centropodia forskalii, Cornulaca monacantha, Ephedra alata var. alenda, Euphorbia guyoniana, Helianthemum confertum, Henophyton deserti, Moltkiopsis ciliata and Spartidium saharae were collected from remote areas of North Africa, especially from the Tunisian region of Sahara. After drying and applying the appropriate extraction methods, the plant extracts were tested in antimicrobial screening assay, performed on 19 Gram-positive and -negative strains of microbes. The inhibition zones produced by plant extracts were determined by disc-diffusion method. Remarkable antibacterial activities were exhibited by extracts of Ephedra alata var. alenda and Helianthemum confertum against B. subtilis, M. catarrhalis and methicillin-resistant and non-resistant S. aureus. Minimum inhibitory concentrations of these two species were also determined. Antiproliferative effects of the extracts were evaluated against 4 human adherent cell lines (HeLa, A431, A2780 and MCF7). Notable cell growth inhibition was found for extract of Helianthemum confertum and Euphorbia guyoniana. Our results provided data for selection of some plant species for further detailed pharmacological and phytochemical examinations.

A study on the effects of the estrous cycle on uterine fluid and blood serum immunoglobulin G (IgG content in the cow

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Sayed Mortaza Alavi-Shoushtari

2014-06-01

Full Text Available To investigate the IgG content and its variations in uterine fluid (UF during the estrous cycle of the cow and to compare them with those of the blood serum (S, six pairs of serum and UF samples for each phase of the cycle selected out of 240 bovine genital tracts and blood samples were collected from Urmia abattoir. The UF samples were collected by gentle scraping of the endometrium using a curette after uterine incision and their IgG content and those of the serum were measured by single radial immuno-diffusion (SRID assay. Serum IgG values (Mean ± SEM were generally higher than the UF values throughout the cycle except for di-estrus (S: 38.50 ± 0.90, UF: 51.60 ± 2.10 mg mL-1, in which the highest values were observed in UF samples. In met-estrus the difference was not significant (S: 34.80 ± 1.80mg mL-1, UF: 30.80 ± 5.20 mg mL-1, however, in estrus the mean UF IgG value (12.50 ± 1.10 mg mL-1 was lower than that of the serum (31.30 ± 1.20 mg mL-1. In pro-estrus, the lowest values (S: 27.80 ± 1.30 mg mL-1, UF: 9.10 ± 1.50 mg mL-1 were obtained. The results showed a lower IgG values in the bovine UF than those of the serum in the follicular phase of the cycle, while in di-estrus the UF IgG content was the highest, suggesting some IgG production in the uterus at this phase.

Influence de la variété, du temps de stockage et du taux de natron sur la cuisson des graines de niébé

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Balla, A.

2006-01-01

Full Text Available Influence of Variety, Storage Time and Natron Percentage on the Cooking Time of Cowpea Vigna unguiculata Seed. The present study is focussed on the influence of the variety, the time of storage and the natron percentage on the cooking time of cowpea seed. Firstly, a physicochemical analysis has been made on the four retained varieties. Then a test of cooking to the water of these different varieties has been achieved. Of the gotten results, it comes out again that the cooking time depends on the varieties. Among the used varieties, the KVX 30- 309-6G cooks 30 minutes after boiling point, while the TN 27-80 requires a maximum time of 40 minutes. This study also shows that the time of storage influences the cooking time of the seeds. The oldest seeds cook less quickly and also present an index swelling more important. Finally this work shows that the use of the natron decreases the cooking time of the dry beans. However, a dose critical of natron beyond which all increase of the natron is without effect on the cooking time exists. On the nutritional plan one observes that the use of the natron in the water of cooking brings mineral elements notably of the Na+ ions that can have a damaging effect on health when the dose is high.

Modeling and optimization of poly(3hydroxybutyrate-co-3hydroxyvalerate) production from cane molasses by Azohydromonas lata MTCC 2311 in a stirred-tank reactor: effect of agitation and aeration regimes.

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Zafar, Mohd; Kumar, Shashi; Kumar, Surendra; Dhiman, Amit K

2012-07-01

The effects of agitation and aeration rates on copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] production by Azohydromonas lata MTCC 2311 using cane molasses supplemented with propionic acid in a bioreactor were investigated. The experiments were conducted in a three-level factorial design by varying the impeller (150-500 rev min(-1)) and aeration (0.5-1.5 vvm) rates. Further, the data were fitted to mathematical models [quadratic polynomial equation and artificial neural network (ANN)] and process variables were optimized by genetic algorithm-coupled models. ANN and hybrid ANN-GA were found superior for modeling and optimization of process variables, respectively. The maximum copolymer concentration of 7.45 g l(-1) with 21.50 mol% of 3HV was predicted at process variables: agitation speed, 287 rev min(-1); and aeration rate, 0.85 vvm, which upon validation gave 7.20 g l(-1) of P(3HB-co-3HV) with 21 mol% of 3HV with the prediction error (%) of 3.38 and 2.32, respectively. Agitation speed established a relative high importance of 72.19% than of aeration rate (27.80%) for copolymer accumulation. The volumetric gas-liquid mass transfer coefficient (k (L) a) was strongly affected by agitation and aeration rates. The highest P(3HB-co-3HV) productivity of 0.163 g l(-1) h(-1) was achieved at 0.17 s(-1) of k (L) a value. During the early phase of copolymer production process, 3HB monomers were accumulated, which were shifted to 3HV units (9-21%) during the cultivation period of 24-42 h. The enhancement of 7.5 and 34% were reported for P(3HB-co-3HV) production and 3HV content, respectively, by hybrid ANN-GA paradigm, which revealed the significant utilization of cane molasses for improved copolymer production.

Experimental investigations into the spectral reflectivity and emissivity of liquid UO2, UC, ThO2, and Nd2O3

International Nuclear Information System (INIS)

Karow, H.U.; Bober, M.

1979-01-01

Fast reactor safety research requires knowledge of emissivity data of nuclear fuel materials up to temperatures of the liquid state. A special integrating sphere laser reflectometer has been used to measure the normal reflectivity and emissivity of UO 2 , UC, ThO 2 , and in addition of Nd 2 O 3 in the solid state (premolten, refrozen material) and in the liquid state up to temperatures of 4000 to 4800 K. The measuring wavelengths have been 0.63 μm and 10.6 μm. The emissivity curves of the oxidic specimens measured at 0.63 μm show the same characteristic course: little temperature dependence below the melting point, distinct increase in the liquid state. In the case of UO 2 the emissivity at the melting point (3120 K) is 0.84, at 4100 K it is 0.92. At 10.6 μm, a decrease has been measured for the liquid state of UO 2 and ThO 2 . UC shows in the solid and in the liquid state only a small temperature dependence with a marked drop, however, at the melting point (2780 K) from 0.54 to 0.45. The measuring results are presented by diagrams and by fit equations related to the true and the black temperature, respectively. (orig./HP) [de

The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests.

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Keleştimur, F; Aksu, A

1996-01-01

The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

Green Chemistry Approach for Synthesis of Effective Anticancer Palladium Nanoparticles.

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Gurunathan, Sangiliyandi; Kim, EunSu; Han, Jae Woong; Park, Jung Hyun; Kim, Jin-Hoi

2015-12-15

The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs) using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis) spectroscopy was used to monitor the conversion of Pd(II) ions to Pd(0)NPs. X-ray diffraction (XRD) revealed the crystallinity of the as-synthesized PdNPs and Fourier transform infrared spectroscopy (FTIR) further confirmed the role of the leaf extract of Evolvulus alsinoides as a reducing and stabilizing agent for the synthesis of PdNPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that the average size of the NPs was 5 nm. After a 24-h exposure to PdNPs, cell viability and light microscopy assays revealed the dose-dependent toxicity of the PdNPs. Furthermore, the dose-dependent cytotoxicity of the PdNPs was confirmed by lactate dehydrogenase (LDH), increased reactive oxygen species (ROS) generation, activation of PdNPs-induced autophagy, impairment of mitochondrial membrane potential (MMP), enhanced caspase-3 activity, and detection of TUNEL-positive cells. Our study demonstrates a single, simple, dependable and green approach for the synthesis of PdNPs using leaf extracts of Evolvulus alsinoides. Furthermore, the in vitro efficacy of PdNPs in human ovarian cancer cells suggests that it could be an effective therapeutic agent for cancer therapy.

Treatment and disposal of refinery sludges: Indian scenario.

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Bhattacharyya, J K; Shekdar, A V

2003-06-01

Crude oil is a major source of energy and feedstock for petrochemicals. Oily sludge, bio-sludge and chemical sludge are the major sludges generated from the processes and effluent treatment plants of the refineries engaged in crude oil refining operations. Refineries in India generate about 28,220 tons of sludge per annum. Various types of pollutants like phenols, heavy metals, etc. are present in the sludges and they are treated as hazardous waste. Oily sludge, which is generated in much higher amount compared to other sludges, contains phenol (90-100 mg/kg), nickel (17-25 mg/kg), chromium (27-80 mg/kg), zinc (7-80 mg/kg), manganese (19-24 mg/kg), cadmium (0.8-2 mg/kg), copper (32-120 mg/kg) and lead (0.001-0.12 mg/ kg). Uncontrolled disposal practices of sludges in India cause degradation of environmental and depreciation of aesthetic quality. Environmental impact due to improper sludge management has also been identified. Salient features of various treatment and disposal practices have been discussed. Findings of a case study undertaken by the authors for Numaligarh Refinery in India have been presented. Various system alternatives have been identified for waste management in Numaligarh Refinery. A ranking exercise has been carried out to evaluate the alternatives and select the appropriate one. A detailed design of the selected waste management system has been presented.

Young infants with severe tetralogy of Fallot: Early primary surgery versus transcatheter palliation.

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Wilder, Travis J; Van Arsdell, Glen S; Benson, Lee; Pham-Hung, Eric; Gritti, Michael; Page, Alexandra; Caldarone, Christopher A; Hickey, Edward J

2017-11-01

Infants with severe tetralogy of Fallot may undergo (1) early primary surgical repair (EARLY) or (2) early transcatheter palliation (CATH) before delayed surgical repair. We compared these strategies with (3) elective single-stage tetralogy of Fallot repair (IDEAL). From 2000 to 2012, 453 children underwent tetralogy of Fallot repair (excluding systemic-pulmonary shunts), including 383 in the IDEAL (75%), 42 in the EARLY (9%), and 28 in the CATH (6%) groups. IDEAL repair at The Hospital for Sick Children occurs after 3 months. Risk-adjusted hazard analysis compared freedom from surgical or catheter reintervention. Somatic size, branch pulmonary artery size, and right ventricle systolic pressure were modeled using 2780 echocardiogram reports via mixed-model regression. CATH involved right ventricular outflow tract stent in 18 patients, right ventricular outflow tract balloon in 9 patients, and ductal-stent in 1 patient. Three patients died (1 per group). Risk-adjusted freedom from surgical reoperation was 89% ± 4%, 88% ± 5%, and 85% ± 6% for the IDEAL, EARLY, and CATH groups, respectively, at 10 years. Patients in the EARLY and CATH groups had similar reoperation rates, except for neonates (tetralogy of Fallot. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Evaluation of enamel mineral loss around cavities prepared by the Er,Cr:YSGG laser and restored with different materials

Science.gov (United States)

Navarro, Ricardo Scarparo; Lago, Andréa. Dias Neves; Bonifácio, Clarissa Calil; Mendes, Fausto Medeiros; de Freitas, Patrícia Moreira; Baptista, Alessandra; Nunez, Silvia Cristina; Matos, Adriana Bona; Imparato, José Carlos P.

2018-02-01

The aim of this study was to evaluate the enamel demineralization around cavities prepared by Er,Cr:YSGG laser (2780 nm) and restored with different materials after an acid challenge. The human dental enamel samples were randomly divided in 12 groups (n=10): G1- high-speed drill (HD); G2- Er,Cr:YSGG laser L (3 W, 20 Hz, 53.05 J/cm2)(air 65% - water 55%); G3- L (4 W, 20 Hz, 70.74 J/cm2); G4- L (5 W, 20 Hz, 88.43 J/cm2). Each group was divided in subgroups: 1- glass ionomer cement (GIC), 2- resin modified GIC (RMGIC), 3- composite resin (C). Samples were submitted to an acid challenge (4.8 pH) for7 days. The calcium ion contend (ppm/mm2) from demineralizing solutions were analyzed by atomic emission spectrometry. ANOVA and LSD tests were performed (α=5%). The significant lower average values of calcium loss were observed on G2 + GIC, G2 + RMGIC, G1 + RMGIC (penamel demineralization. The findings of this in vitro study suggest that the Er,Cr:YSGG lased cavities restored with GIC or RMGIC or conventional drill cavities with RMGIC were effective on reducing the demineralization around restorations, showing an important potential in preventing secondary caries.

Exploring the potential of phyllosilicate minerals as potassium fertilizers using sodium tetraphenylboron and intensive cropping with perennial ryegrass

Science.gov (United States)

Li, Ting; Wang, Huoyan; Wang, Jing; Zhou, Zijun; Zhou, Jianmin

2015-01-01

In response to addressing potassium (K) deficiency in soil and decreasing agricultural production costs, the potential of K-bearing phyllosilicate minerals that can be directly used as an alternative K source has been investigated using sodium tetraphenylboron (NaTPB) extraction and an intensive cropping experiment. The results showed that the critical value of K-release rate and leaf K concentration was 3.30 g kg−1 h−1 and 30.64 g (kg dry matter)−1, respectively under the experimental conditions. According to this critical value, the maximum amount of released K that could be utilized by a plant with no K deficiency symptoms was from biotite (27.80 g kg−1) and vermiculite (5.58 g kg−1), followed by illite, smectite and muscovite with 2.76, 0.88 and 0.49 g kg−1, respectively. Ryegrass grown on phlogopite showed K deficiency symptoms during the overall growth period. It is concluded that biotite and vermiculite can be directly applied as a promising and sustainable alternative to the use of classical K fertilizers, illite can be utilized in combination with soluble K fertilizers, whereas muscovite, phlogopite and smectite may not be suitable for plant growth. Further field experiments are needed to assess the use of these phyllosilicate minerals as sources of K fertilizer. PMID:25782771

Preparation and quality evaluation of LHRHa-targeted Brucea javanica oil liposomes

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Xiao-juan LIU

2013-07-01

Full Text Available Objective　To prepare luteinizing hormone-releasing hormone a (LHRHa targeted Bruceajavanicaliposomes and evaluate its quality. Methods　The LHRHa-targeted Bruceajavanicaliposome was prepared by thin layer dispersion together with biotin¬streptavidin bridge method. The optimum formation was selected by means of orthogonal design of experiment. The morphology of liposome was observed with transmission electron microscope. Zetasizer Nano ZS analyzer was used to measure the particle size and zeta potential. The entrapment efficiency was determined by ultra-violet spectroscopy and column chromatography. Centrifugal acceleration experiment and determination of leak rate were performed to prove the liposome stability. The targeting ability of liposome was appraised by cell experiment in vitro. Results　The formed optimum formula was as follows: the ratio of lecithin to cholesterol was 4:1, Brucea javanicaoil:lipid was 3:10, DSPE-PEG (2000-Biotin:lecithin content was 3%, ultrasonic-homogenized for 8 minutes. Liposomes were round in shape, the average diameter and zeta potential of liposome were 155.1±14.5mm and –(24.1±0.54 mV, respectively. The average entrapment efficiency was 92.2%. Binding capacity with the A2780/DDP cell line in the LHRHa-targeted liposomes was 2.7 times higher than that in the non-targeting liposomes. Conclusion　The technique of preparing LHRHa-targeted Bruceajavanicaliposome is suitable, and high in entrapment efficiency, with good stability and targeting ability.

Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells

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Yoon Jin Cho

2016-09-01

Full Text Available Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G1 population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

On-line double isotope dilution laser ablation inductively coupled plasma mass spectrometry for the quantitative analysis of solid materials.

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Fernández, Beatriz; Rodríguez-González, Pablo; García Alonso, J Ignacio; Malherbe, Julien; García-Fonseca, Sergio; Pereiro, Rosario; Sanz-Medel, Alfredo

2014-12-03

We report on the determination of trace elements in solid samples by the combination of on-line double isotope dilution and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The proposed method requires the sequential analysis of the sample and a certified natural abundance standard by on-line IDMS using the same isotopically-enriched spike solution. In this way, the mass fraction of the analyte in the sample can be directly referred to the certified standard so the previous characterization of the spike solution is not required. To validate the procedure, Sr, Rb and Pb were determined in certified reference materials with different matrices, including silicate glasses (SRM 610, 612 and 614) and powdered samples (PACS-2, SRM 2710a, SRM 1944, SRM 2702 and SRM 2780). The analysis of powdered samples was carried out both by the preparation of pressed pellets and by lithium borate fusion. Experimental results for the analysis of powdered samples were in agreement with the certified values for all materials. Relative standard deviations in the range of 6-21% for pressed pellets and 3-21% for fused solids were obtained from n=3 independent measurements. Minimal sample preparation, data treatment and consumption of the isotopically-enriched isotopes are the main advantages of the method over previously reported approaches. Copyright © 2014 Elsevier B.V. All rights reserved.

Contributions to a shallow aquifer study by reprocessed seismic sections from petroleum exploration surveys, eastern Abu Dhabi, United Arab Emirates

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Woodward, D.

1994-01-01

The US Geological Survey, in cooperation with the National Drilling Company of Abu Dhabi, is conducting a 4-year study of the fresh and slightly saline groundwater resources of the eastern Abu Dhabi Emirate. Most of this water occurs in a shallow aquifer, generally less than 150 m deep, in the Al Ain area. A critical part of the Al Ain area coincides with a former petroleum concession area where about 2780 km of vibroseis data were collected along 94 seismic lines during 1981-1983. Field methods, acquistion parameters, and section processing were originally designed to enhance reflections expected at depths ranging from 5000 to 6000 m, and subsurface features directly associated with the shallow aquifer system were deleted from the original seismic sections. The original field tapes from the vibroseis survey were reprocessed in an attempt to extract shallow subsurface information (depths less than 550 m) for investigating the shallow aquifer. A unique sequence of reproccessing parameters was established after reviewing the results from many experimental tests. Many enhancements to the resolution of shallow seismic reflections resulted from: (1) application of a 20-Hz, low-cut filter; (2) recomputation of static corrections to a datum nearer the land surface; (3) intensive velocity analyses; and (4) near-trace muting analyses. The number, resolution, and lateral continuity of shallow reflections were greatly enhanced on the reprocessed sections, as was the delineation of shallow, major faults. Reflections on a synthetic seismogram, created from a borehole drilled to a depth of 786 m on seismic line IQS-11, matcheddprecisely with shallow reflections on the reprocessed section. The 33 reprocessed sections were instrumental in preparing a map showing the major structural features that affect the shallow aquifer system. Analysis of the map provides a better understanding of the effect of these shallow features on the regional occurrence, movement, and quality of

Kinetic Modeling of Arsenic Cycling by a Freshwater Cyanobacterium as Influenced by N:P Ratios: A Potential Biologic Control in an Iron-Limited Drainage Basin

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Markley, C. T.; Herbert, B. E.

2004-12-01

Elevated As levels are common in South Texas surface waters, where As is derived from the natural weathering of geogenic sources and a byproduct of historical uranium mining. The impacted surface waters of the Nueces River drainage basin supply Lake Corpus Christi (LCC), a major drinking water reservoir for the Corpus Christi area. The soils and sediments of the Nueces River drainage basin generally have low levels of reactive iron (average concentration of 2780 mg/kg), limiting the control of iron oxyhydroxides on As geochemistry and bioavailability. Given these conditions, biologic cycling of As may have a large influence on As fate and transport in LCC. Sediment cores from LCC show evidence for cyanobacterial blooms after reservoir formation based upon stable isotopes, total organic matter and specific elemental correlations. While algae have been shown to accumulate and reduce inorganic As(V), few studies have reported biologic cycling of As by cyanobacteria. Therefore, As(V) uptake, accumulation, reduction, and excretion in a 1.0 μ M As(V) solution by the freshwater cyanobacterium, Anabaena sp. Strain PCC 7120, was measured over time as a function of low, middle and high N:P ratios (1.2, 12, 120) to determine nutrient effects on As cycling by the cyanobacterium. Total As(V) reduction was observed in all three conditions upon completion of the ten-day experiment. Maximum As(V) reduction rates ranged from (0.013 mmol g C-1 day-1) in the low N:P solution to (0.398 mmol g C-1 day-1) in the high N:P solution. Increased cell biomass in the low N:P ratio solution compensated for the low maximum reduction rate to allow total As(V) reduction. Kinetic equations commonly used to model algal-nutrient interactions were utilized in modeling the current data. The Michaelis-Menten enzyme saturation equation modified with a competitive inhibition term adequately modeled As(III) excretion in the high and middle N:P ratio test conditions. The low N:P test condition further

Increased atrial natriuretic factor receptor density in cultured vascular smooth muscle cells of the spontaneously hypertensive rat

International Nuclear Information System (INIS)

Khalil, F.; Fine, B.; Kuriyama, S.; Hatori, N.; Nakamura, A.; Nakamura, M.; Aviv, A.

1987-01-01

To explore the role of the atrial natriuretic factor (ANF) system in the pathophysiology of hypertension we examined the binding kinetics of synthetic ANF to cultured vascular smooth muscle cells (VSMCs) derived from the spontaneously hypertensive rat (SHR) and two normotensive controls-the Wistar Kyoto (WKY) and American Wistar (W). The number of maximal binding sites (Bmax) per cell (mean +/- SEM; X10(3] were: SHR = 278.0 +/- 33.0, WKY = 28.3 +/- 7.1 and W = 26.6 +/- 4.2. The differences between the SHR and normotensive strains were significant at p less than 0.001. The equilibrium dissociation constant (Kd; X 10(-9)M) was higher in SHR VSMCs (0.94 +/- 0.14) than in WKY (0.22 +/- 0.09; p less than 0.01) and W (0.39 +/- 0.14; p less than 0.02) cells. The plasma levels of the immunoreactive ANF were higher in SHR than the normotensive controls. We suggest that the relatively greater ANF receptor density in cultured VSMCs of the SHR represents a response to the in vitro environment which is relatively more deficient in ANF for VSMCs of the SHR as compared with the normotensive rats. Thus, the capacity of the SHR VSMC to regulate ANF receptor density appears to be independent of the blood pressure level

Molecular Characterization of Putative Virulence Determinants in Burkholderia pseudomallei

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Suat Moi Puah

2014-01-01

Full Text Available The Gram-negative saprophyte Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease which is endemic in Southeast Asia and northern Australia. This bacterium possesses many virulence factors which are thought to contribute to its survival and pathogenicity. Using a virulent clinical isolate of B. pseudomallei and an attenuated strain of the same B. pseudomallei isolate, 6 genes BPSL2033, BP1026B_I2784, BP1026B_I2780, BURPS1106A_A0094, BURPS1106A_1131, and BURPS1710A_1419 were identified earlier by PCR-based subtractive hybridization. These genes were extensively characterized at the molecular level, together with an additional gene BPSL3147 that had been identified by other investigators. Through a reverse genetic approach, single-gene knockout mutants were successfully constructed by using site-specific insertion mutagenesis and were confirmed by PCR. BPSL2033::Km and BURPS1710A_1419::Km mutants showed reduced rates of survival inside macrophage RAW 264.7 cells and also low levels of virulence in the nematode infection model. BPSL2033::Km demonstrated weak statistical significance (P=0.049 at 8 hours after infection in macrophage infection study but this was not seen in BURPS1710A_1419::Km. Nevertheless, complemented strains of both genes were able to partially restore the gene defects in both in vitro and in vivo studies, thus suggesting that they individually play a minor role in the virulence of B. pseudomallei.

Tetrathiomolybdate sensitizes ovarian cancer cells to anticancer drugs doxorubicin, fenretinide, 5-fluorouracil and mitomycin C

International Nuclear Information System (INIS)

Kim, Kyu Kwang; Lange, Thilo S; Singh, Rakesh K; Brard, Laurent; Moore, Richard G

2012-01-01

Our recent study showed that tetrathiomolybdate (TM), a drug to treat copper overload disorders, can sensitize drug-resistant endometrial cancer cells to reactive oxygen species (ROS)-generating anticancer drug doxorubicin. To expand these findings in the present study we explore TM efficacy in combination with a spectrum of ROS-generating anticancer drugs including mitomycin C, fenretinide, 5-fluorouracil and doxorubicin in ovarian cancer cells as a model system. The effects of TM alone or in combination with doxorubicin, mitomycin C, fenretinide, or 5-fluorouracil were evaluated using a sulforhodamine B assay. Flow cytometry was used to detect the induction of apoptosis and ROS generation. Immunoblot analysis was carried out to investigate changes in signaling pathways. TM potentiated doxorubicin-induced cytotoxicity and modulated key regulators of apoptosis (PARP, caspases, JNK and p38 MAPK) in SKOV-3 and A2780 ovarian cancer cell lines. These effects were linked to the increased production of ROS, as shown in SKOV-3 cells. ROS scavenging by ascorbic acid blocked the sensitization of cells by TM. TM also sensitized SKOV-3 to mitomycin C, fenretinide, and 5-fluorouracil. The increased cytotoxicity of these drugs in combination with TM was correlated with the activity of ROS, loss of a pro-survival factor (e.g. XIAP) and the appearance of a pro-apoptotic marker (e.g. PARP cleavage). Our data show that TM increases the efficacy of various anticancer drugs in ovarian cancer cells in a ROS-dependent manner

Oxidative stress induces monocyte necrosis with enrichment of cell-bound albumin and overexpression of endoplasmic reticulum and mitochondrial chaperones.

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Haiping Tang

Full Text Available In the present study, monocytes were treated with 5-azacytidine (azacytidine, gossypol or hydrogen peroxide to induce cell death through oxidative stress. A shift from apoptotic to necrotic cell death occurred when monocytes were treated with 100 µM azacytidine for more than 12 hours. Necrotic monocytes exhibited characteristics, including enrichment of cell-bound albumin and up-regulation of endoplasmic reticulum (ER- and mitochondrial-specific chaperones to protect mitochondrial integrity, which were not observed in other necrotic cells, including HUH-7, A2780, A549 and HOC1a. Our results show that the cell-bound albumin originates in the culture medium rather than from monocyte-derived hepatocytes, and that HSP60 is a potential binding partner of the cell-bound albumin. Proteomic analysis shows that HSP60 and protein disulfide isomerase are the most abundant up-regulated mitochondrial and ER-chaperones, and that both HSP60 and calreticulin are ubiquitinated in necrotic monocytes. In contrast, expression levels of the cytosolic chaperones HSP90 and HSP71 were down-regulated in the azacytidine-treated monocytes, concomitant with an increase in the levels of these chaperones in the cell culture medium. Collectively, our results demonstrates that chaperones from different organelles behave differently in necrotic monocytes, ER- and mitochondrial chaperones being retained and cytosolic and nuclear chaperones being released into the cell culture medium through the ruptured cell membrane. HSP60 may serve as a new target for development of myeloid leukemia treatment.

The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis

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Qiu, Jun-jun [Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011 (China); Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032 (China); Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011 (China); Wang, Yan [Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong' an Road, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong' an Road, Shanghai 200032 (China); Ding, Jing-xin; Jin, Hong-yan [Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011 (China); Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032 (China); Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011 (China); Yang, Gong, E-mail: yanggong@fudan.edu.cn [Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong' an Road, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong' an Road, Shanghai 200032 (China); Hua, Ke-qin, E-mail: huakeqin@126.com [Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011 (China); Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032 (China); Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011 (China)

2015-05-01

HOX transcript antisense RNA (HOTAIR) is a well-known long non-coding RNA (lncRNA) whose dysregulation correlates with poor prognosis and malignant progression in many forms of cancer. Here, we investigate the expression pattern, clinical significance, and biological function of HOTAIR in serous ovarian cancer (SOC). Clinically, we found that HOTAIR levels were overexpressed in SOC tissues compared with normal controls and that HOTAIR overexpression was correlated with an advanced FIGO stage and a high histological grade. Multivariate analysis revealed that HOTAIR is an independent prognostic factor for predicting overall survival in SOC patients. We demonstrated that HOTAIR silencing inhibited A2780 and OVCA429 SOC cell proliferation in vitro and that the anti-proliferative effects of HOTAIR silencing also occurred in vivo. Further investigation into the mechanisms responsible for the growth inhibitory effects by HOTAIR silencing revealed that its knockdown resulted in the induction of cell cycle arrest and apoptosis through certain cell cycle-related and apoptosis-related proteins. Together, these results highlight a critical role of HOTAIR in SOC cell proliferation and contribute to a better understanding of the importance of dysregulated lncRNAs in SOC progression. - Highlights: • HOTAIR overexpression correlates with an aggressive tumour phenotype and a poor prognosis in SOC. • HOTAIR promotes SOC cell proliferation both in vitro and in vivo. • The proliferative role of HOTAIR is associated with regulation of the cell cycle and apoptosis.

Role of dihydrotestosterone (DHT) on TGF-β1 signaling pathway in epithelial ovarian cancer cells.

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Kohan-Ivani, Karla; Gabler, Fernando; Selman, Alberto; Vega, Margarita; Romero, Carmen

2016-01-01

One of the hypotheses regarding the genesis of epithelial ovarian cancer involves the action of androgens on the proliferation of epithelial ovarian cells, as well as inclusion cysts. The purpose of the present study was to evaluate whether DHT causes changes in the TGF-β1 pathway that might modify the anti-proliferative effect of the latter. The levels of TGF-β1 protein, of its receptors (TGFBR1 and TGFBR2), of Smad2/3 (canonical signaling pathway protein) and of p21 (cell cycle protein) were assessed in ovarian tissues, epithelial ovarian cancer cell lines (A2780) and control cell lines (HOSE) through the use of immunohistochemistry and immunocytochemistry. Additionally, cell lines were treated with 100 nmol/L DHT, 10 ng/mL of TGF-β1 and DHT + TGF-β1 during 72 h in the presence and absence of a siRNA against androgen receptor. After treatment, TGFBR1 and TGFBR2 levels were detected through Western blotting and p21 was assessed through immunocytochemistry. Epithelial ovarian cancer tissues showed a decrease in TGF-β1 I receptor (p DHT, protein levels of TGF-β1 receptors (TGFBR1-TGFBR2) showed a decrease (p DHT (p < 0.001). Overall, our results indicate a defect in the canonical TGF-β signaling pathway in epithelial ovarian cancer caused by androgen action, thus suggesting eventual changes in such tissue proliferation rates.

Transcatheter arterial embolization for upper gastrointestinal tract bleeding.

Science.gov (United States)

Širvinskas, Audrius; Smolskas, Edgaras; Mikelis, Kipras; Brimienė, Vilma; Brimas, Gintautas

2017-12-01

Transcatheter arterial embolization is a possible treatment for patients with recurrent bleeding from the upper gastrointestinal tract after failed endoscopic management and is also an alternative to surgical treatment. To analyze the outcomes of transcatheter arterial embolization and identify the clinical and technical factors that influenced the rates of morbidity and mortality. A retrospective analysis was carried out, based on the data of 36 patients who underwent transcatheter arterial embolization for acute nonvariceal upper gastrointestinal bleeding in 2013 to 2015 in our center. An analysis was performed between early rebleeding rates, mortality and the following factors: patient sex, age, number of units of packed red blood cells and packed plasma administered to the patients, length of hospital stay, therapeutic or prophylactic embolization. The technical success rate of the embolization procedure was 100%. There were 15 (41.70%) therapeutic embolizations and 21 (58.3%) prophylactic embolizations. There was a 77.8% clinical success rate. Following embolization, 10 (27.80%) patients had repeated bleeding and 9 (25.0%) patients died. Significant associations were found between rebleeding and prophylactic embolization (OR = 10.53; p = 0.04) and between mortality and prophylactic embolization (OR = 10.53; p = 0.04) and units of packed red blood cells (OR = 1.25; p < 0.01). In our experience, transcatheter arterial embolization is a safe treatment method for acute nonvariceal upper gastrointestinal bleeding and a possible alternative to surgery for high-risk patients.

Problematic Internet Use in University Students: associated factors and differences of gender.

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Fernández-Villa, Tania; Alguacil Ojeda, Juan; Almaraz Gómez, Ana; Cancela Carral, José María; Delgado-Rodríguez, Miguel; García-Martín, Miguel; Jiménez-Mejías, Eladio; Llorca, Javier; Molina, Antonio José; Ortíz Moncada, Rocío; Valero-Juan, Luiz Félix; Martín, Vicente

2015-12-15

The aim of this paper is to make a descriptive analysis of Problematic Internet Use in college students, evaluating the possible association with health problems and addictive behaviors, as well as gender differences in user types. A total of 2,780 students participated in the study between 2011 and 2014, 29% of them being males (age 20.8 ± 5.1 years) and 71% females (age 20.3 ± 4.4 years). The prevalence of Problematic Internet Use (PIU) assessed by the Internet Addiction Test was 6.08%. Being under 21 years of age and studying for degrees in subjects other than the health sciences were associated factors with a higher frequency of this problem, no differences by gender or type of address were found. The results show a significant association with some health problems (migraines, back pain, excess weight or obesity, insufficient rest), psychological aspects (risk of eating disorders, risk of mental disorder, depression), family problems and discrimination; with no associations with substance use (alcohol, cannabis or tobacco) being found. Concerning the time of Internet use, weekly hours were significantly higher in women than in men, both the total time as for leisure. The analysis of the profile use in problematic users revealed that males are related to aspects of entertainment such as games or shopping online and females are related to aspects of socialization, such as chats and social networks.

Green Chemistry Approach for Synthesis of Effective Anticancer Palladium Nanoparticles

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Sangiliyandi Gurunathan

2015-12-01

Full Text Available The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis spectroscopy was used to monitor the conversion of Pd(II ions to Pd(0NPs. X-ray diffraction (XRD revealed the crystallinity of the as-synthesized PdNPs and Fourier transform infrared spectroscopy (FTIR further confirmed the role of the leaf extract of Evolvulus alsinoides as a reducing and stabilizing agent for the synthesis of PdNPs. Dynamic light scattering (DLS and transmission electron microscopy (TEM showed that the average size of the NPs was 5 nm. After a 24-h exposure to PdNPs, cell viability and light microscopy assays revealed the dose-dependent toxicity of the PdNPs. Furthermore, the dose-dependent cytotoxicity of the PdNPs was confirmed by lactate dehydrogenase (LDH, increased reactive oxygen species (ROS generation, activation of PdNPs-induced autophagy, impairment of mitochondrial membrane potential (MMP, enhanced caspase-3 activity, and detection of TUNEL-positive cells. Our study demonstrates a single, simple, dependable and green approach for the synthesis of PdNPs using leaf extracts of Evolvulus alsinoides. Furthermore, the in vitro efficacy of PdNPs in human ovarian cancer cells suggests that it could be an effective therapeutic agent for cancer therapy.

Risk assessment of genotoxic and carcinogenic alkenylbenzenes in botanical containing products present on the Chinese market.

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Ning, Jia; Cui, XinYue; Kong, XiangNan; Tang, YiFei; Wulandari, Riana; Chen, Lu; Wesseling, Sebas; Rietjens, Ivonne M C M

2018-03-15

In the present study, a risk assessment of plant food supplements (PFS), traditional Chinese medicines (TCM) and herbal teas containing alkenylbenzenes was performed using the Margin of Exposure (MOE) approach. The levels of alkenylbenzenes in botanical preparations collected on the Chinese market were quantified and the combined estimated daily intake (EDI) was determined using dose additivity. The combined EDI values obtained assuming equal potency of all alkenylbenzenes detected in the PFS, TCM and herbal teas were 0.3 to 14.3, 0.05 to 539.4 and 0.04 to 42.5 μg/kg bw/day, respectively. Calculating combined EDI values taking into account the toxic equivalency (TEQ) approach, the values for PFS, TCM and herbal teas were 0.3 to 7.7, 0.05 to 278.0 and 0.02 to 16.5 μg estragole equivalents/kg bw/day, respectively. The MOE values resulting from consumption of these PFS, TCM and one cup of herbal tea per day during life-time were generally lower than 10 000, suggesting a potential priority for risk management. For short-term exposure such as two weeks consumption, applying Haber's rule, only one TCM 6 () still had an MOE value below 10 000. It is concluded that selected consumption of Chinese botanical preparations raise a concern because of exposure to alkenylbenzenes, especially when exposure is for longer periods of time. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Polyphenolic Compounds and Antioxidant Activity of Cold-Pressed Seed Oil from Finola Cultivar of Cannabis sativa L.

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Smeriglio, Antonella; Galati, Enza M; Monforte, Maria T; Lanuzza, Francesco; D'Angelo, Valeria; Circosta, Clara

2016-08-01

The aim of this study was to characterize the polyphenolic compounds and antioxidant activity of cold-pressed seed oil from Finola cultivar of industrial hemp (Cannabis sativa L.). Several methodologies have been employed to evaluate the in vitro antioxidant activity of Finola hempseed oil (FHSO) and both lipophilic (LF) and hydrophilic fractions (HF). The qualitative and quantitative composition of the phenolic fraction of FHSO was performed by HPLC analyses. From the results is evident that FHSO has high antioxidative activity, as measured by DPPH radical (146.76 mmol of TE/100 g oil), inhibited β-carotene bleaching, quenched a chemically generated peroxyl radical in vitro and showed high ferrous ion chelating activity. Reactivity towards 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation and ferric-reducing antioxidant power values were 695.2 µmol of TE/100g oil and 3690.6 µmol of TE/100 g oil respectively. FHSO contains a significant amount of phenolic compounds of which 2780.4 mg of quercetin equivalent/100 g of total flavonoids. The whole oil showed higher antioxidant activity compared with LF and HF. Our findings indicate that the significant antioxidant properties shown from Finola seed oil might generally depend on the phenolic compounds, especially flavonoids, such as flavanones, flavonols, flavanols and isoflavones. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Causes of death in critically ill multiple sclerosis patients.

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Karamyan, A; Brandtner, H; Grinzinger, S; Chroust, V; Bacher, C; Otto, F; Reisp, M; Hauer, L; Sellner, J

2017-10-01

Patients with multiple sclerosis (MS) experience higher mortality rates as compared to the general population. While the risk of intensive care unit (ICU) admission is also reported to be higher, little is known about causes of death CoD in critically ill MS patients. To study the causes of death (CoD) in the series of critically ill patients with MS verified by autopsy. We reviewed hospital electronic charts of MS patients treated at the neurological ICU of a tertiary care hospital between 2000 and 2015. We compared clinical and pathological CoD for those who were autopsied. Overall, 10 patients were identified (seven female; median age at death 65 years, range 27-80), and six of them were autopsied. The median MS duration prior to ICU admission was 27.5 years (range 1-50), and the median EDSS score at the time of ICU admission was 9 (range 5-9.5). The median length of ICU stay was 3 days (range 2-213). All the individuals in our series had experienced respiratory insufficiency during their ICU stay. The autopsy examination of brain tissue did not reveal evidences of MS lesions in one patient. In another patient, Lewy bodies were found on brain immunohistochemistry. Mortality in critically ill MS patients is largely driven by respiratory complications. Sporadic disparities between clinical and pathological findings can be expected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk indicator for agricultural inputs of trace elements to Canadian soils.

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Sheppard, S C; Grant, C A; Sheppard, M I; de Jong, R; Long, J

2009-01-01

Trace elements (TEs) are universally present in environmental media, including soil, but agriculture uses some materials that have increased TE concentrations. Some TEs (e.g., Cu, Se, and Zn) are added to animal feeds to ensure animal health. Similarly, TEs are present in micronutrient fertilizers. In the case of phosphate fertilizers, some TEs (e.g., Cd) may be inadvertently elevated because of the source rock used in the manufacturing. The key question for agriculture is "After decades of use, could these TE additions result in the deterioration of soil quality?" An early warning would allow the development of best management practices to slow or reverse this trend. This paper discusses a model that estimates future TE concentrations for the 2780 land area polygons composing essentially all of the agricultural land in Canada. The development of the model is discussed, as are various metrics to express the risk related to TE accumulation. The elements As, Cd, Cu, Pb, Se, and Zn are considered, with inputs from the atmosphere, fertilizers, manures, and municipal biosolids. In many cases, steady-state concentrations could be toxic, but steady state is far in the future. In 100 yr, the soil concentrations (Century soil concentrations) are estimated to be up to threefold higher than present background, an impact even if not a problematic impact. The geographic distribution reflects agricultural intensity. Contributions from micronutrient fertilizers are perhaps the most uncertain due to the limited data available on their use.

Three New Cytotoxic ent-Kaurane Diterpenes from Isodon excisoides

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Li-Ping Dai

2015-09-01

Full Text Available Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1; 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2; and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3; together with six known diterpenes henryin (4; kamebanin (5; reniformin C (6; kamebacetal A (7; kamebacetal B (8; and oridonin (9. The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC50 values ranging from 1.09–8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC50 values ranging from 1.31–2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity.

IND-2, a pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline derivative, circumvents multi-drug resistance and causes apoptosis in colon cancer cells.

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Karthikeyan, Chandrabose; Lee, Crystal; Moore, Joshua; Mittal, Roopali; Suswam, Esther A; Abbott, Kodye L; Pondugula, Satyanarayana R; Manne, Upender; Narayanan, Narayanan K; Trivedi, Piyush; Tiwari, Amit K

2015-02-01

Naturally occurring condensed quinolines have anticancer properties. In efforts to find active analogues, we designed and synthesized eight polycyclic heterocycles with a pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline framework (IND series). The compounds were evaluated for activity against colon (HCT-116 and S1-MI-80), prostate (PC3 and DU-145), breast (MCF-7 and MDAMB-231), ovarian (ov2008 and A2780), and hepatocellular (HepG2) cancer cells and against non-cancerous Madin Darby canine kidney (MDCK), mouse embryonic fibroblast (NIH/3T3), and human embryonic kidney cells (HEK293). IND-2, a 4-chloro-2-methyl pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline, exhibited more than ten-fold selectivity and potent cytotoxic activity against colon cancer cells relative to the other cancer and non-cancer cells. With five additional colon cancer cell lines (HT-29, HCT-15, LS-180, LS-174, and LoVo), IND-2 had similar cytotoxicity and selectivity, and sub-micromolar concentrations caused changes in the morphology of HCT-116 and HCT-15 cells. IND-2 did not activate the transactivating function of the pregnane X receptor (PXR), indicating that it does not induce PXR-regulated ABCB1 or ABCG2 transporters. Indeed, IND-2 was not a substrate of ABCB1 or ABCG2, and it induced cytotoxicity in HEK293 cells overexpressing ABCB1 or ABCG2 to the same extent as in normal HEK293 cells. IND-2 was cytotoxic to resistant colon carcinoma S1-MI-80 cells, approximately three- and five-fold more than SN-38 and topotecan, respectively. In HCT-116 colon cancer cells, IND-2 produced concentration-dependent changes in mitochondrial membrane potential, leading to apoptosis, and sub-micromolar concentrations caused chromosomal DNA fragmentation. These findings suggest that, by increasing apoptosis, IND-2 has potential therapeutic efficacy for colorectal cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT inhibition on human cancer cells.

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Vladimir Tolstikov

Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer and HCT-116 (colorectal cancer cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA, and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS.

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Almeida, Gilberto S; Bawn, Carlo M; Galler, Martin; Wilson, Ian; Thomas, Huw D; Kyle, Suzanne; Curtin, Nicola J; Newell, David R; Maxwell, Ross J

2017-09-01

Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ( 1 H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD + ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild-type (WT) and PARP1 knock-out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. 1 H-MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD + levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD + levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD + levels in the temozolomide-treated group. The combination of rucaparib and temozolomide did not prevent the NAD + depletion caused by temozolomide treatment. The 1 H-MRS results show that NAD + levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD + would be valuable. Copyright © 2017 John Wiley & Sons, Ltd.

Triterpenoidal saponins from the fruits of Gleditsia caspica with proapoptotic properties.

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Shaheen, Usama; Ragab, Ehab A; Abdalla, Ashraf N; Bader, Ammar

2018-01-01

Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were isolated from the fruits of Gleditsia caspica Desf. The aglycons of these saponins were echinocystic acid, erythrodiol and 12-oleanene-3,28,30-triol. Caspicaoside L is a bisdesmosidic saponin acylated with two monoterpenic acids. It has a disaccharide moiety made up of glucose and arabinose attached to C-3 and pentasaccharide moiety linked to C-28 made up of one glucose, 2 xyloses, one inner rhamnose and one terminal rhamnose which was acylated with two identical monoterpenic acids. Caspicaoside M is a monodesmosidic saponin with a trisaccharide moiety at C-3 made up of glucose, xylose and arabinose, while caspicaoside N has a disaccharide moiety at C-3 made up of glucose and arabinose. Their structures were determined by extensive 1D and 2D (DQF-COSY, HSQC, TOCSY, 1 H- 13 C-HSQC-TOCSY, HMBC, ROESY, NOESY) NMR, HRESIMS analyses and chemical degradation. The cytotoxicity MTT-based assay showed that caspicaosides M, N and L, respectively, exhibited high cytotoxic activity with IC 50  ≤ 10 μM (72 h) at least against one of the three used cancer cell lines, MCF 7, A2780 and HT 29; and were 2-34 folds selective against the normal fibroblasts (MRC 5). All compounds also induced apoptosis and caused G 2 /M arrest in MCF 7 cells (24 h); thus showing pro-apoptotic properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

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Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

2017-12-01

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

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Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

2017-11-01

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

[Changes in knowledge, attitudes, and smoking behavior among young people in Germany. Results of repeated, representative surveys by the BZgA].

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Orth, B; Töppich, J

2010-02-01

Following an increase in tobacco consumption among 12 to 17 year olds between 1993 and 1997, a policy mix comprising various structural and behavioral prevention measures was implemented in Germany. One element of this policy mix is the "rauchfrei" ("smoke-free") youth campaign of the BZgA (Federal Centre for Health Education), a combination of media that reaches a large number of youth, personal communication, and setting-based interventions. The aim is to prevent young people from starting to smoke and to promote the cessation of smoking at an early stage. Based on a multistage intervention model, wide coverage of the measures should be achieved among young people, as well as changes in knowledge, attitudes, social norms, and behavioral intentions. Based on the intervention model, repeated, representative cross-sectional surveys were conducted to examine the development of these indicators and of tobacco consumption. Five studies were conducted during the period from 2003 to 2008, each comprising between 1,220 and 2,780 computer-assisted telephone interviews with randomly selected young people between the ages of 12 and 17. The percentage of young people reached by information offered on the subject of not smoking rose between 2003 and 2008. Participation in school-based prevention measures also rose. There was an increase in knowledge regarding the harmful substances contained in cigarette smoke, and in the percentage of young people who rated active and passive smoking as being harmful to health. In addition, the attitude towards smoking of young people who have never smoked became more critical, as did that perceived in the social environment. The proportion of young people who smoke declined substantially, from 27.5% (2001) to 15.4% (2008), and there was been a major rise in the number who have never smoked, from 40.5% (2001) to 60.6% (2008). The change in knowledge-based risk assessments, attitudes, and social norms should be further promoted by mass media

Incidence and risk factors of hypomagnesemia in head and neck cancer patients treated with cetuximab

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Tomohiro Enokida

2016-09-01

Full Text Available Background Hypomagnesemia is a common adverse event during cetuximab (Cmab treatment. However, few reports have investigated the incidence and risk factors of hypomagnesemia in head and neck cancer patients treated with Cmab. Methods We retrospectively reviewed 131 head and neck cancer patients who received Cmab-containing therapy. Main eligibility criteria were ≥3 Cmab administrations, no prior EGFR-directed therapy, and no prophylactic Mg supplementation.Results Median baseline serum Mg level and number of Cmab administrations were 2.2 mg/dl and eight, respectively. Overall incidence of hypomagnesemia was 50.4% (grade 1, 46.6%; grade 2, 3.1%; grade 3, 0%; grade 4, 0.8% and differed between patients treated with palliative chemotherapy and bioradiation (Cmab and radiation (63% vs. 24%; p<0.01. Independent risk factors were low baseline serum Mg [Odds ratio (OR 161.988, 95% confidence interval (CI 9.436-2780.895], ≥7 Cmab administrations (OR 3.56, 95% CI 1.16-13.98, and concurrent administration of platinum (cisplatin; OR 23.695, 95% CI 5.219-107.574, carboplatin; OR 5.487, 95% CI 1.831-16.439. Respective incidence of hypomagnesemia in patients in high- (concurrent platinum and ≥7 Cmab administrations and low-risk (no concurrent platinum and <7 Cmab administrations groups was 66.0% and 6.6% (P<0.001, OR 28.0. Conclusion Cmab is associated with a significant risk of hypomagnesemia in patients with head and neck cancer with longer term administration and concurrent platinum therapy. High-risk patients should be treated with particular care.

The relationship between Internet addiction and depression among migrant children and left-behind children in China.

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Guo, Jing; Chen, Li; Wang, Xiaohua; Liu, Yan; Chui, Cheryl Hiu Kwan; He, Huan; Qu, Zhiyong; Tian, Donghua

2012-11-01

With greater Internet availability, the pathological use of the Internet has become an emerging mental health issue among adolescents in China. The objective of this study was to examine the associations between Internet addiction and depression in migrant children (MC) and left-behind children (LBC). The present study was conducted using a cross-sectional design with 3,254 participants (8-17-years old), which included 1143 LBC, 574 MC, and 1287 nonleft-behind rural children (RC) from 12 schools. Young's 8-item Internet Addiction Scale was used to assess Internet dependency. The Children's Depression Inventory-Short Form was used to measure child depression. The results showed that the prevalence of depression was 10.9 percent among RC, 19.7 percent among MC, and 14.3 percent among LBC. The prevalence of Internet addiction was 3.7 percent among RC, and was 6.4 percent among MC and 3.2 percent among LBC. Depression was effected by the interaction between types of children and Internet addiction. LBC with Internet addiction (odds ratio [OR], 2.780; 95 percent confidence interval [CI], 1.237-6.248), MC with Internet addiction (OR, 2.922; 95 percent CI, 1.116-7.652), and MC with no Internet addiction (OR, 2.735; 95 percent CI, 1.974-3.789) had higher risks of depression than that for RC with no-Internet addiction. The results indicated that Internet addiction might be associated with an increased risk of depression in LBC, and migration was an important risk factor for child depression.

Sacrococcygeal pilonidal disease: analysis of previously proposed risk factors

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Ali Harlak

2010-01-01

Full Text Available PURPOSE: Sacrococcygeal pilonidal disease is a source of one of the most common surgical problems among young adults. While male gender, obesity, occupations requiring sitting, deep natal clefts, excessive body hair, poor body hygiene and excessive sweating are described as the main risk factors for this disease, most of these need to be verified with a clinical trial. The present study aimed to evaluate the value and effect of these factors on pilonidal disease. METHOD: Previously proposed main risk factors were evaluated in a prospective case control study that included 587 patients with pilonidal disease and 2,780 healthy control patients. RESULTS: Stiffness of body hair, number of baths and time spent seated per day were the three most predictive risk factors. Adjusted odds ratios were 9.23, 6.33 and 4.03, respectively (p<0.001. With an adjusted odds ratio of 1.3 (p<.001, body mass index was another risk factor. Family history was not statistically different between the groups and there was no specific occupation associated with the disease. CONCLUSIONS: Hairy people who sit down for more than six hours a day and those who take a bath two or less times per week are at a 219-fold increased risk for sacrococcygeal pilonidal disease than those without these risk factors. For people with a great deal of hair, there is a greater need for them to clean their intergluteal sulcus. People who engage in work that requires sitting in a seat for long periods of time should choose more comfortable seats and should also try to stand whenever possible.

Reconstruction of late Quaternary relative humidity changes on the southern slopes of Mt. Kilimanjaro, East Africa, using a coupled δ2H-δ18O biomarker paleohygrometer

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Hepp, Johannes; Zech, Roland; Rozanski, Kazimierz; Tuthorn, Mario; Glaser, Bruno; Greule, Markus; Keppler, Frank; Huang, Yongsong; Zech, Wolfgang; Zech, Michael

2016-04-01

Our understanding of African paleoclimate/-hydrological history is decisively based on lake level and lake sediment studies. It furthermore improved remarkably during the last decade thanks to emerging stable isotope techniques such as compound-specific deuterium analysis of sedimentary leaf wax biomarkers (δ2Hleaf wax). Here we present results from a multi-proxy biomarker study carried out on a ~100 ka paleosol sequence developed in the Maundi crater at ~2780 m a.s.l. on the southeastern slopes of Mt. Kilimanjaro in equatorial East Africa. The Maundi stable isotope records established for hemicellulose-derived sugars, lignin- and pectin-derived methoxyl groups and leaf wax-derived fatty acid and n-alkane biomarkers (δ18Osugars, δ2Hmethoxyl groups, δ2Hfatty acids and δ2Hn-alkanes) reveal differences but also similar patterns. Maxima characterize the period from 70 to 60 ka, the last glacial maximum (LGM) and the Younger Dryas (YD), whereas minima occur during the Holocene. The application of a 'coupled δ2Hn-alkane-δ18Osugar paleohygrometer' allows the reconstruction of the Late Quaternary relative humidity (RH) history of the Maundi study site. Accordingly, the reconstructed RH changes are well in agreement with the Maundi pollen results. Apart from the overall regional moisture availability, the intensification versus weakening of the trade wind inversion, which affects the diurnal montane atmospheric circulation on the slopes of Mt. Kilimanjaro, is suggested as local second important factor controlling the RH history at Maundi. Furthermore, the Maundi results of the coupled δ2Hn-alkane-δ18Osugar approach caution against interpreting δ2Hleaf wax (as well as δ18Osugar) records straight forwards in terms of reflecting δ2Hprec, because variably and primarily RH-dependent isotopic evapotranspirative enrichment of leaf water can mask δ2Hprec changes. Concerning the biomarker-based reconstructed Maundi δ2H/δ18Oprec record, the comparison with the

Effects of hypoxia on human cancer cell line chemosensitivity

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2013-01-01

Background Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia. Methods A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA). Results Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs. Conclusions A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia. PMID:23829203

Long-term outcome of elderly patients requiring intensive care admission for abdominal pathologies: survival and quality of life.

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Merlani, P; Chenaud, C; Mariotti, N; Ricou, B

2007-05-01

Medical developments have allowed the management of patients aged over 70 years with severe abdominal pathologies requiring intensive care unit (ICU) admission. These patients require enhanced life support and present a high ICU mortality. We investigated the outcome and quality of life (QOL) of elderly patients 2 years after their ICU stay for abdominal pathologies. Patients aged 70 years or over with abdominal pathologies, admitted to our ICU over a period of 2 years, were included. Two years following their ICU stay, a letter informed the patients about the present study. Consent to participate was obtained by telephone. QOL was assessed by the Euro-QOL and Short Form-36 questionnaires. Other patient-centered outcomes were evaluated. Overall, 2780 patients were admitted to the ICU during the study period; 141 (5%) patients were eligible; 112 of the 141 (79%) survived their ICU stay, 95 (67%) survived their hospital stay and 52 (37%) were alive 2 years after their ICU stay; 36 of the 52 survivors (69%) answered the questionnaire. Their QOL 2 years after their ICU stay was decreased in comparison with an age-matched population. Eighty-one per cent of patients lived at home and 57% were totally independent. They perceived their ICU stay as positive and 75% stated that they would agree to go through intensive care again. Factors associated with 2-year survival were the absence of co-morbidity, absence of malignancy and a lower Simplified Acute Physiology II score on ICU admission. A high mortality rate and a decrease in QOL were observed in elderly patients with severe abdominal pathologies. Nonetheless, these patients were able to adapt well to their physical disabilities.

Increase in soil stable carbon isotope ratio relates to loss of organic carbon: results from five long-term bare fallow experiments.

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Menichetti, Lorenzo; Houot, Sabine; van Oort, Folkert; Kätterer, Thomas; Christensen, Bent T; Chenu, Claire; Barré, Pierre; Vasilyeva, Nadezda A; Ekblad, Alf

2015-03-01

Changes in the (12)C/(13)C ratio (expressed as δ(13)C) of soil organic C (SOC) has been observed over long time scales and with depth in soil profiles. The changes are ascribed to the different reaction kinetics of (12)C and (13)C isotopes and the different isotopic composition of various SOC pool components. However, experimental verification of the subtle isotopic shifts associated with SOC turnover under field conditions is scarce. We determined δ(13)C and SOC in soil sampled during 1929-2009 in the Ap-horizon of five European long-term bare fallow experiments kept without C inputs for 27-80 years and covering a latitudinal range of 11°. The bare fallow soils lost 33-65% of their initial SOC content and showed a mean annual δ(13)C increase of 0.008-0.024‰. The (13)C enrichment could be related empirically to SOC losses by a Rayleigh distillation equation. A more complex mechanistic relationship was also examined. The overall estimate of the fractionation coefficient (ε) was -1.2 ± 0.3‰. This coefficient represents an important input to studies of long-term SOC dynamics in agricultural soils that are based on variations in (13)C natural abundance. The variance of ε may be ascribed to site characteristics not disclosed in our study, but the very similar kinetics measured across our five experimental sites suggest that overall site-specific factors (including climate) had a marginal influence and that it may be possible to isolate a general mechanism causing the enrichment, although pre-fallow land use may have some impact on isotope abundance and fractionation.

Folate-conjugated polymeric micelle HB-loaded on targeting effect by intraperitoneal to ovarian cancer in vitro and in vivo.

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Li, Jie; Yao, Shu; Wang, Kai; Lu, Zaijun; Su, Xuantao; Li, Li; Yuan, Cunzhong; Feng, Jinbo; Yan, Shi; Kong, Beihua; Song, Kun

2018-04-04

Photodynamic therapy (PDT) is considered as an innovative and attractive modality to treat ovarian cancer. In this study, a biodegradable polymer poly (ethylene glycol)-poly (lactic acid)(PLA)-folate (FA-PEG-PLA) was prepared in order to synthesize an active targeting, water soluble and pharmacomodulated photosensitizer nano-carriers. The drug loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which HB/FA-PEG-PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (pHB/FA-PEG-PLA micelles, the cellular uptake study in vitro were tested, which owned significantly enhanced uptake of HB/FA-PEG-PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR-). The enhanced uptake of HB/FA-PEG-PLA micelles to cancer cells resulted in a more effective post-PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA-PEG-PLA micelles by SKOV3 cells were also observed in vivo after intraperitoneal injection of folate targeted micelles in tumor-bearing ascitic ovarian cancer animals. The drug levels in ascitic tumor tissues were increased by 20-fold (pHB-loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results demonstrated that our new developed PDT photosensitizer HB/FA-PEG-PLA micelles has a high drug-loading capacity, good biocompatibility, control drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

CARS microscopy for the monitoring of lipid storage in C. elegans

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Enejder, Annika; Brackmann, Christian; Axäng, Claes; Åkeson, Madeleine; Pilon, Marc

2008-02-01

After several years of proof-of-principle measurements and focus on technological development, it is timely to make full use of the capabilities of CARS microscopy within the biosciences. We have here identified an urgent biological problem, to which CARS microscopy provides unique insights and consequently may become a widely accepted experimental procedure. In order to improve present understanding of mechanisms underlying dysfunctional metabolism regulation reported for many of our most wide-spread diseases (obesity, diabetes, cardio-vascular diseases etc.), we have monitored genetic and environmental impacts on cellular lipid storage in the model organism C. elegans in vivo in a full-scale biological study. Important advantages of CARS microscopy could be demonstrated compared to present technology, i.e. fluorescence microscopy of labelled lipid stores. The fluorescence signal varies not only with the presence of lipids, but also with the systemic distribution of the fluorophore and the chemical properties of the surrounding medium. By instead probing high-density regions of CH bonds naturally occurring in the sample, the CARS process was shown to provide a consistent representation of the lipid stores. The increased accumulation of lipid stores in mutants with deficiencies in the insulin and transforming growth factor signalling pathways could hereby be visualized and quantified. Furthermore, spectral CARS microscopy measurements in the C-H bond region of 2780-2930 cm -1 provided the interesting observation that this accumulation comes with a shift in the ordering of the lipids from gel- to liquid phase. The present study illustrates that CARS microscopy has a strong potential to become an important instrument for systemic studies of lipid storage mechanisms in living organisms, providing new insights into the phenomena underlying metabolic disorders.

Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line

International Nuclear Information System (INIS)

Vaskivuo, Liisa; Rysae, Jaana; Koivuperae, Johanna; Myllynen, Paeivi; Vaskivuo, Tommi; Chvalova, Katerina; Serpi, Raisa; Savolainen, Eeva-Riitta; Puistola, Ulla; Vaehaekangas, Kirsi

2006-01-01

p14 ARF tumor suppressor protein regulates p53 by interfering with mdm2-p53 interaction. p14 ARF is activated in response to oncogenic stimuli but little is known of the responses of endogenous p14 ARF to different types of cellular stress or DNA damage. Azidothymidine (AZT) is being tested in several clinical trials as an enhancer of anticancer chemotherapy. However, the knowledge of the relationship between AZT and cellular pathways, e.g. p53 pathway, is very limited. In this study, we show that AZT, cisplatin (CDDP) and docetaxel (DTX) all induce unique molecular responses in OVCAR-3 ovarian carcinoma cells carrying a mutated p53, while in A2780, ovarian carcinoma and MCF-7 breast carcinoma cells with wild type p53, all of these drugs cause similar p53 responses. We found that endogenous p14 ARF protein in OVCAR-3 cells is down-regulated by DTX but induced by AZT and a short CDDP pulse treatment. In HT-29 colon carcinoma cells with a mutated p53, all treatments down-regulated p14 ARF protein. Both CDDP and AZT increased the expression of p14ARF mRNA in OVCAR-3 cells. Differences in cell death induced by these drugs did not explain the differences in protein and mRNA expressions. No increase in the level of either c-Myc or H-ras oncoproteins was seen in OVCAR-3 cells after AZT or CDDP-treatment. These results suggest that p14 ARF can respond to DNA damage without oncogene activation in cell lines without functional p53

The impact of pediatric obesity on hospitalized children with lower respiratory tract infections in the United States.

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Okubo, Yusuke; Nochioka, Kotaro; Testa, Marcia A

2018-04-01

Obesity is the most common public health problem and is a clinically complicating risk factor among hospitalized children. The impact of pediatric obesity on the severity and morbidity of lower respiratory tract infections remains unclear. We conducted a retrospective cohort study of bronchitis and pneumonia among children aged 2-20 years using hospital discharge records. The data were obtained from the Kid's Inpatient Database in 2003, 2006, 2009, and 2012, and were weighted to estimate the number of hospitalizations in the United States. We used the International Classification of Diseases, Ninth Revision, Clinical Modification code (278.0×) to classify whether the patient was obese or not. We investigated the associations between pediatric obesity and use of mechanical ventilation using multivariable logistic regression model. In addition, we ascertained the relationships between pediatric obesity, comorbid blood stream infections, mean healthcare cost, and length of hospital stay. We estimated a total of 133 602 hospitalizations with pneumonia and bronchitis among children aged between 2 and 20 years. Obesity was significantly associated with use of mechanical ventilation (adjusted OR 2.90, 95% CI 2.15-3.90), comorbid bacteremia or septicemia (adjusted OR 1.58, 95% CI 1.03-2.44), elevated healthcare costs (adjusted difference $383, 95%CI $276-$476), and prolonged length of hospital stay (difference 0.32 days, 95%CI 0.23-0.40 days), after adjusting for patient and hospital characteristics using multivariable logistic regression models. Pediatric obesity is an independent risk factor for severity and morbidity among pediatric patients with lower respiratory tract infections. These findings suggest the importance of obesity prevention for pediatric populations. © 2017 John Wiley & Sons Ltd.

Integrated modeling of the dynamic meteorological and sea surface conditions during the passage of Typhoon Morakot

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Lee, Han Soo; Yamashita, Takao; Hsu, John R.-C.; Ding, Fei

2013-01-01

In August 2009, Typhoon Morakot caused massive flooding and devastating mudslides in the southern Taiwan triggered by extremely heavy rainfall (2777 mm in 4 days) which occurred during its passage. It was one of the deadliest typhoons that have ever attacked Taiwan in recent years. In this study, numerical simulations are performed for the storm surge and ocean surface waves, together with dynamic meteorological fields such as wind, pressure and precipitation induced by Typhoon Morakot, using an atmosphere-waves-ocean integrated modelling system. The wave-induced dissipation stress from breaking waves, whitecapping and depth-induced wave breaking, is parameterized and included in the wave-current interaction process, in addition to its influence on the storm surge level in shallow water along the coast of Taiwan. The simulated wind and pressure field captures the characteristics of the observed meteorological field. The spatial distribution of the accumulated rainfall within 4 days, from 00:00 UTC 6 August to 00:00 UTC 10 August 2009, shows similar patterns as the observed values. The 4-day accumulated rainfall of 2777 mm at the A-Li Shan mountain weather station for the same period depicted a high correlation with the observed value of 2780 mm/4 days. The effects of wave-induced dissipation stress in the wave-current interaction resulted in increased surge heights on the relatively shallow western coast of Taiwan, where the bottom slope of the bathymetry ranges from mild to moderate. The results also show that wave-breaking has to be considered for accurate storm surge prediction along the east coast of Taiwan over the narrow bank of surf zone with a high horizontal resolution of the model domain.

Human umbilical blood mononuclear cell-derived mesenchymal stem cells serve as interleukin-21 gene delivery vehicles for epithelial ovarian cancer therapy in nude mice.

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Hu, Weihua; Wang, Jing; He, Xiangfeng; Zhang, Hongyi; Yu, Fangliu; Jiang, Longwei; Chen, Dengyu; Chen, Junsong; Dou, Jun

2011-01-01

Ovarian cancer causes more deaths than any other cancer of the female reproductive system, and its overall cure rate remains low. The present study investigated human umbilical blood mononuclear cell (UBMC)-derived mesenchymal stem cells (UBMC-MSCs) as interleukin-21 (IL-21) gene delivery vehicles for ovarian cancer therapy in nude mice. MSCs were isolated from UBMCs and the expanded cells were phenotyped by flow cytometry. Cultured UBMCs were differentiated into osteocytes and adipocytes using appropriate media and then the UBMC-MSCs were transfected with recombinant pIRES2-IL-21-enhancement green fluorescent protein. UBMC-MSCs expressing IL-21 were named as UBMC-MSC-IL-21. Mice with A2780 ovarian cancer were treated with UBMC-MSC-IL-21 intravenously, and the therapeutic efficacy was evaluated by the tumor volume and mouse survival. To address the mechanism of UBMC-MSC-IL-21 against ovarian cancer, the expression of IL-21, natural killer glucoprotein 2 domain and major histocompatibility complex class I chain-related molecules A/B were detected in UBMC-MSC-IL-21 and in the tumor sites. Interferon-γ-secreting splenocyte numbers and natural killer cytotoxicity were significantly increased in the UBMC-MSC-IL-21-treated mice as compared with the UBMC-MSCs or the UBMC-MSC-mock plasmid-treated mice. Most notably, tumor growth was delayed and survival was prolonged in ovarian-cancer-bearing mice treated with UBMC-MSC-IL-21. Our data provide important evidence that UBMC-MSCs can serve as vehicles for IL-21 gene delivery and inhibit the established tumor. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Methane Production by Seagrass Ecosystems in the Red Sea

KAUST Repository

Garcias Bonet, Neus; Duarte, Carlos M.

2017-01-01

Atmospheric methane (CH) is the second strongest greenhouse gas and it is emitted to the atmosphere naturally by different sources. It is crucial to define the dimension of these natural emissions in order to forecast changes in atmospheric CH mixing ratio in future scenarios. However, CH emissions by seagrass ecosystems in shallow marine coastal systems have been neglected although their global extension. Here we quantify the CH production rates of seagrass ecosystems in the Red Sea. We measured changes in CH concentration and its isotopic signature by cavity ring-down spectroscopy on chambers containing sediment and plants. We detected CH production in all the seagrass stations with an average rate of 85.09 ± 27.80 μmol CH m d. Our results show that there is no seasonal or daily pattern in the CH production rates by seagrass ecosystems in the Red Sea. Taking in account the range of global estimates for seagrass coverage and the average seagrass CH production, the global CH production and emission by seagrass ecosystems could range from 0.09 to 2.7 Tg yr. Because CH emission by seagrass ecosystems had not been included in previous global CH budgets, our estimate would increase the contribution of marine global emissions, hitherto estimated at 9.1 Tg yr, by about 30%. Thus, the potential contribution of seagrass ecosystems to marine CH emissions provides sufficient evidence of the relevance of these fluxes as to include seagrass ecosystems in future assessments of the global CH budgets.

Methane Production by Seagrass Ecosystems in the Red Sea

KAUST Repository

Garcias Bonet, Neus

2017-11-07

Atmospheric methane (CH) is the second strongest greenhouse gas and it is emitted to the atmosphere naturally by different sources. It is crucial to define the dimension of these natural emissions in order to forecast changes in atmospheric CH mixing ratio in future scenarios. However, CH emissions by seagrass ecosystems in shallow marine coastal systems have been neglected although their global extension. Here we quantify the CH production rates of seagrass ecosystems in the Red Sea. We measured changes in CH concentration and its isotopic signature by cavity ring-down spectroscopy on chambers containing sediment and plants. We detected CH production in all the seagrass stations with an average rate of 85.09 ± 27.80 μmol CH m d. Our results show that there is no seasonal or daily pattern in the CH production rates by seagrass ecosystems in the Red Sea. Taking in account the range of global estimates for seagrass coverage and the average seagrass CH production, the global CH production and emission by seagrass ecosystems could range from 0.09 to 2.7 Tg yr. Because CH emission by seagrass ecosystems had not been included in previous global CH budgets, our estimate would increase the contribution of marine global emissions, hitherto estimated at 9.1 Tg yr, by about 30%. Thus, the potential contribution of seagrass ecosystems to marine CH emissions provides sufficient evidence of the relevance of these fluxes as to include seagrass ecosystems in future assessments of the global CH budgets.

Characteristics of the dairy goat primary sector at the Rio de Janeiro State, Brazil Características do setor primário da caprinocultura leiteira no estado do Rio de Janeiro, Brasil

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Edizio Santos Junior

2008-04-01

Full Text Available A survey was done based on 19 goat shepherds at counties of Centre-highlands, Northern and North-western regions of the Rio de Janeiro State and at the county of Pedra Dourada, Zona da Mata region, State of Minas Gerais. We aimed to characterise the primary sector of the goat milk production chain settled at those regions. Therefore, questionnaires were applied in order to depict profiles of the shepherds, their families, the role of the wife in the activity, the resources available, dependence on income generated by the activity, and how producers administrate their business. Farms were distributed in five strata according to the following daily milk production averages and standard deviations: 8.8 ± 0.9, 15.7 ± 3.9, 22.6 ± 2.7, 34.4 ± 3.4, and 183.8 ± 54.2 L/d. Approximately 42% of the interviewed producers conducted their activities according to a household production model and the income earned was exclusively from the dairy goat husbandry. Sons and daughters performed an important role in the business (27.80%, but most of them (62.73% worked out at non farm activities. The percentage of wives that worked directly in the activity (@47% indicated that it could contribute to gender equity in the rural environment. Most of the production systems (63.16% presented positive gross margins. We have noticed, however, that shepherds perceived only the business gross margin and that the most accurate registries taken were those related to revenues. In general, producers of the higher strata were favoured by their larger production scale, but asymptotic behaviours for costs and amounts invested in animals, equipments and buildings were observed. These characteristics should be considered when policies related to the dairy goat primary sector have to be planned.Realizou-se um levantamento com base em 19 caprinoculturas de municípios das regiões Centro-Serrana, Norte e Noroeste do estado do Rio de Janeiro e do município de Pedra Dourada, regi

Challenges in microarray class discovery: a comprehensive examination of normalization, gene selection and clustering

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Landfors Mattias

2010-10-01

Full Text Available Abstract Background Cluster analysis, and in particular hierarchical clustering, is widely used to extract information from gene expression data. The aim is to discover new classes, or sub-classes, of either individuals or genes. Performing a cluster analysis commonly involve decisions on how to; handle missing values, standardize the data and select genes. In addition, pre-processing, involving various types of filtration and normalization procedures, can have an effect on the ability to discover biologically relevant classes. Here we consider cluster analysis in a broad sense and perform a comprehensive evaluation that covers several aspects of cluster analyses, including normalization. Result We evaluated 2780 cluster analysis methods on seven publicly available 2-channel microarray data sets with common reference designs. Each cluster analysis method differed in data normalization (5 normalizations were considered, missing value imputation (2, standardization of data (2, gene selection (19 or clustering method (11. The cluster analyses are evaluated using known classes, such as cancer types, and the adjusted Rand index. The performances of the different analyses vary between the data sets and it is difficult to give general recommendations. However, normalization, gene selection and clustering method are all variables that have a significant impact on the performance. In particular, gene selection is important and it is generally necessary to include a relatively large number of genes in order to get good performance. Selecting genes with high standard deviation or using principal component analysis are shown to be the preferred gene selection methods. Hierarchical clustering using Ward's method, k-means clustering and Mclust are the clustering methods considered in this paper that achieves the highest adjusted Rand. Normalization can have a significant positive impact on the ability to cluster individuals, and there are indications that

Challenges in microarray class discovery: a comprehensive examination of normalization, gene selection and clustering

Science.gov (United States)

2010-01-01

Background Cluster analysis, and in particular hierarchical clustering, is widely used to extract information from gene expression data. The aim is to discover new classes, or sub-classes, of either individuals or genes. Performing a cluster analysis commonly involve decisions on how to; handle missing values, standardize the data and select genes. In addition, pre-processing, involving various types of filtration and normalization procedures, can have an effect on the ability to discover biologically relevant classes. Here we consider cluster analysis in a broad sense and perform a comprehensive evaluation that covers several aspects of cluster analyses, including normalization. Result We evaluated 2780 cluster analysis methods on seven publicly available 2-channel microarray data sets with common reference designs. Each cluster analysis method differed in data normalization (5 normalizations were considered), missing value imputation (2), standardization of data (2), gene selection (19) or clustering method (11). The cluster analyses are evaluated using known classes, such as cancer types, and the adjusted Rand index. The performances of the different analyses vary between the data sets and it is difficult to give general recommendations. However, normalization, gene selection and clustering method are all variables that have a significant impact on the performance. In particular, gene selection is important and it is generally necessary to include a relatively large number of genes in order to get good performance. Selecting genes with high standard deviation or using principal component analysis are shown to be the preferred gene selection methods. Hierarchical clustering using Ward's method, k-means clustering and Mclust are the clustering methods considered in this paper that achieves the highest adjusted Rand. Normalization can have a significant positive impact on the ability to cluster individuals, and there are indications that background correction is

ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19

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Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V.; Dion, Patrick A.; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A.; Williams, Kelly L.; Blair, Ian P.; Nicholson, Garth A.; Gonzalez-Perez, Paloma; Brown, Robert H.; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A.; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3–5 years from onset. Familial ALS (FALS) comprises 5%–10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. PMID:24119685

Expression of the glioma-associated oncogene homolog 1 (gli1 in advanced serous ovarian cancer is associated with unfavorable overall survival.

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Alessandra Ciucci

Full Text Available Recent evidence links aberrant activation of Hedgehog (Hh signaling with the pathogenesis of several cancers including medulloblastoma, glioblastoma, melanoma as well as pancreas, colorectal, and prostate carcinomas. Here we investigated the role of the transcription factor Gli1 in ovarian cancer. To this end, the expression profile of Gli1 was examined in normal ovaries, ovarian tumors, and ovarian cancer cell lines, and the in vitro effects of a specific Hh-pathway blocker, KAAD-cyclopamine, or a specific Gli1 inhibitor (GANT58 on cell proliferation and on Hh target gene expression were also assessed. Results obtained showed that epithelial cells in ovarian cancer tissue express significantly higher levels of nuclear Gli1 than in normal ovarian tissue, where the protein was almost undetectable. In addition, multivariate analysis showed that nuclear Gli1 was independently associated to poor survival in advanced serous ovarian cancer patients (HR = 2.2, 95%CI 1.0-5.1, p = 0.04. In vitro experiments demonstrated Gli1 expression in the three ovarian carcinoma cell lines tested, A2780, SKOV-3 and OVCAR-3. Remarkably, although KAAD-cyclopamine led to decreased cell proliferation, this treatment did not inhibit hedgehog target gene expression in any of the three ovarian cancer cell lines, suggesting that the inhibition of cell proliferation was a nonspecific or toxic effect. In line with these data, no differences on cell proliferation were observed when cell lines were treated with GANT58. Overall, our clinical data support the role of Gli1 as a prognostic marker in advanced serous ovarian cancer and as a possible therapeutic target in this disease. However, our in vitro findings draw attention to the need for selection of appropriate experimental models that accurately represent human tumor for testing future therapies involving Hh pathway inhibitors.

Autonomic nervous system dysfunction in children with severe tetanus: dissociation of cardiac and vascular sympathetic control

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Mazzei de Davila C.A.

2003-01-01

Full Text Available The medical records of ten pediatric patients with a clinical diagnosis of tetanus were reviewed retrospectively. The heart rate and blood pressure of all tetanus patients were measured noninvasively every hour during the first two weeks of hospitalization. Six of ten tetanus patients presented clinical evidence of sympathetic hyperactivity (group A and were compared with a control group consisting of four children who required mechanical ventilation for diseases other than tetanus (group B. Heart rate and blood pressure simultaneously and progressively increased to a maximum by day 7. The increase over baseline was 43.70 ± 11.77 bpm (mean ± SD for heart rate (P<0.01 and 38.60 ± 26.40 mmHg for blood pressure (P<0.01. These values were higher and significantly different from those of the control group (group B at day 6, which had an average heart rate increase over baseline of 19.35 ± 12.26 bpm (P<0.05 and blood pressure of 10.24 ± 13.30 mmHg (P<0.05. By the end of the second week of hospitalization, in group A the increase of systolic blood pressure over baseline had diminished to 9.60 ± 15.37 mmHg (P<0.05, but the heart rate continued to be elevated (27.80 ± 33.92 bpm, P = NS, when compared to day 7 maximal values. The dissociation of these two cardiovascular variables at the end of the second week of hospitalization suggests the presence of asymmetric cardiac and vascular sympathetic control. One possible explanation for these observations is a selective and delayed action of tetanus toxin on the inhibitory neurons which control sympathetic outflow to the heart.

Population genetic structure of rare and endangered plants using molecular markers

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Raji, Jennifer; Atkinson, Carter T.

2013-01-01

This study was initiated to assess the levels of genetic diversity and differentiation in the remaining populations of Phyllostegia stachyoides and Melicope zahlbruckneri in Hawai`i Volcanoes National Park and determine the extent of gene flow to identify genetically distinct individuals or groups for conservation purposes. Thirty-six Amplified Fragment Length Polymorphic (AFLP) primer combinations generated a total of 3,242 polymorphic deoxyribonucleic acid (DNA) fragments in the P. stachyoides population with a percentage of polymorphic bands (PPB) ranging from 39.3 to 65.7% and 2,780 for the M. zahlbruckneri population with a PPB of 18.8 to 64.6%. Population differentiation (Fst) of AFLP loci between subpopulations of P. stachyoides was low (0.043) across populations. Analysis of molecular variance of P. stachyoides showed that 4% of the observed genetic differentiation occurred between populations in different kīpuka and 96% when individuals were pooled from all kīpuka. Moderate genetic diversity was detected within the M. zahlbruckneri population. Bayesian and multivariate analyses both classified the P. stachyoides and M. zahlbruckneri populations into genetic groups with considerable sub-structuring detected in the P. stachyoides population. The proportion of genetic differentiation among populations explained by geographical distance was estimated by Mantel tests. No spatial correlation was found between genetic and geographic distances in both populations. Finally, a moderate but significant gene flow that could be attributed to insect or bird-mediated dispersal of pollen across the different kīpuka was observed. The results of this study highlight the utility of a multi-allelic DNA-based marker in screening a large number of polymorphic loci in small and closely related endangered populations and revealed the presence of genetically unique groups of individuals in both M. zahlbruckneri and P. stachyoides populations. Based on these findings

Economic Burden in Chinese Patients with Diabetes Mellitus Using Electronic Insurance Claims Data.

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Yunyu Huang

Full Text Available There is a paucity of studies that focus on the economic burden in daily care in China using electronic health data. The aim of this study is to describe the development of the economic burden of diabetic patients in a sample city in China from 2009 to 2011 using electronic data of patients' claims records.This study is a retrospective, longitudinal study in an open cohort of Chinese patients with diabetes. The patient population consisted of people living in a provincial capital city in east China, covered by the provincial urban employee basic medical insurance (UEBMI. We included any patient who had at least one explicit diabetes diagnosis or received blood glucose lowering medication in at least one registered outpatient visit or hospitalization during a calendar year in the years 2009-2011. Cross-sectional descriptions of different types of costs, prevalence of diabetic complications and related diseases, medication use were performed for each year separately and differences between three years were compared using a chi-square test or the non-parametric Kruskal-Wallis H test.Our results showed an increasing trend in total medical cost (from 2,383 to 2,780 USD, p = 0.032 and diabetes related cost (from 1,655 to 1,857 USD for those diabetic patients during the study period. The diabetes related economic burden was significantly related to the prevalence of complications and related diseases (p<0.001. The overall medication cost during diabetes related visits also increased (from 1,335 to 1,383 USD, p = 0.021. But the use pattern and cost of diabetes-related medication did not show significant changes during the study period.The economic burden of diabetes increased significantly in urban China. It is important to improve the prevention and treatment of diabetes to contribute to the sustainability of the Chinese health-care system.

Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures

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Chan Daniel K

2012-07-01

Full Text Available Abstract Background High mortality rates in ovarian cancer are largely a result of resistance to currently used chemotherapies. Expanding therapies with a variety of drugs has the potential to reduce this high mortality rate. Metformin and phenethyl isothiocyanate (PEITC are both potentially useful in ovarian cancer, and they are particularly attractive because of their safety. Methods Cell proliferation of each drug and drug combination was evaluated by hemacytometry with Trypan blue exclusion or Sytox green staining for cell death. Levels of total and cleaved PARP were measured by Western blot. General cellular and mitochondrial reactive oxygen species were measured by flow cytometry and live cell confocal microscopy with the fluorescent dyes dihydroethidine and MitoSOX. Results Individually, metformin and PEITC each show inhibition of cell growth in multiple ovarian cancer cell lines. Alone, PEITC was also able to induce apoptosis, whereas metformin was primarily growth inhibitory. Both total cellular and mitochondrial reactive oxygen species were increased when treated with either metformin or PEITC. The growth inhibitory effects of metformin were reversed by methyl succinate supplementation, suggesting complex I plays a role in metformin's anti-cancer mechanism. PEITC's anti-cancer effect was reversed by N-acetyl-cysteine supplementation, suggesting PEITC relies on reactive oxygen species generation to induce apoptosis. Metformin and PEITC together showed a synergistic effect on ovarian cancer cell lines, including the cisplatin resistant A2780cis. Conclusions Here we show that when used in combination, these drugs are effective in both slowing cancer cell growth and killing ovarian cancer cells in vitro. Furthermore, the combination of these drugs remains effective in cisplatin resistant cell lines. Novel combinations such as metformin and PEITC show promise in expanding ovarian cancer therapies and overcoming the high incidence of

EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer

International Nuclear Information System (INIS)

Haslehurst, Alexandria M; Weberpals, Johanne; Davey, Scott; Squire, Jeremy; Park, Paul C; Feilotter, Harriet; Koti, Madhuri; Dharsee, Moyez; Nuin, Paulo; Evans, Ken; Geraci, Joseph; Childs, Timothy; Chen, Jian; Li, Jieran

2012-01-01

The epithelial to mesenchymal transition (EMT) is a molecular process through which an epithelial cell undergoes transdifferentiation into a mesenchymal phenotype. The role of EMT in embryogenesis is well-characterized and increasing evidence suggests that elements of the transition may be important in other processes, including metastasis and drug resistance in various different cancers. Agilent 4 × 44 K whole human genome arrays and selected reaction monitoring mass spectrometry were used to investigate mRNA and protein expression in A2780 cisplatin sensitive and resistant cell lines. Invasion and migration were assessed using Boyden chamber assays. Gene knockdown of snail and slug was done using targeted siRNA. Clinical relevance of the EMT pathway was assessed in a cohort of primary ovarian tumours using data from Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. Morphological and phenotypic hallmarks of EMT were identified in the chemoresistant cells. Subsequent gene expression profiling revealed upregulation of EMT-related transcription factors including snail, slug, twist2 and zeb2. Proteomic analysis demonstrated up regulation of Snail and Slug as well as the mesenchymal marker Vimentin, and down regulation of E-cadherin, an epithelial marker. By reducing expression of snail and slug, the mesenchymal phenotype was largely reversed and cells were resensitized to cisplatin. Finally, gene expression data from primary tumours mirrored the finding that an EMT-like pathway is activated in resistant tumours relative to sensitive tumours, suggesting that the involvement of this transition may not be limited to in vitro drug effects. This work strongly suggests that genes associated with EMT may play a significant role in cisplatin resistance in ovarian cancer, therefore potentially leading to the development of predictive biomarkers of drug response or novel therapeutic strategies for overcoming drug resistance

Current disruptions in the near-earth neutral sheet region

International Nuclear Information System (INIS)

Liu, A.T.Y.; Anderson, B.J.; Takahashi, K.; Zanetti, L.J.; McEntire, R.W.; Potemra, T.A.; Lopez, R.E.; Klumpar, D.M.; Greene, E.M.; Strangeway, R.

1992-01-01

Observations from the Charge Composition Explorer in 1985 and 1986 revealed fifteen current disruption events in which the magnetic field fluctuations were large and their onsets coincided well with ground onsets of substorm expansion or intensification. Over the disruption interval, the local magnetic field can change by as much as a factor of ∼7. In general, the stronger the current buildup and the closer the neutral sheet, the larger the resultant field change. There is also a tendency for a larger subsequent enhancement in the AE index with a stronger current buildup prior to current disruption. For events with good pitch angle coverage and extended observation in the neutral sheet region the authors find that the particle pressure increases toward the disruption onset and decreases afterward. Just prior to disruption, either the total particle pressure is isotropic, or the perpendicular component (P perpendicular ) dominates the parallel component (P parallel ), the plasma beta is seen to be as high as ∼70, and the observed plasma pressure gradient at the neutral sheet is large along the tail axis. The deduced local current density associated with pressure gradient is ∼27-80 n/Am 2 and is ∼85-105 mA/m when integrated over the sheet thickness. They infer from these results that just prior to the onset of current disruption, (1) an extremely thin current sheet requiring P parallel > P perpendicular for stress balance does not develop at these distances, (2) the thermal ion orbits are in the chaotic or Speiser regime while the thermal electrons are in the adiabatic regime and, in one case, exhibit peaked fluxes perpendicular to the magnetic field, thus implying no electron orbit chaotization to possibly initiate ion tearing instability, and (3) the neutral sheet is in the unstable regime specified by the cross-field current instability

EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer

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Haslehurst Alexandria M

2012-03-01

Full Text Available Abstract Background The epithelial to mesenchymal transition (EMT is a molecular process through which an epithelial cell undergoes transdifferentiation into a mesenchymal phenotype. The role of EMT in embryogenesis is well-characterized and increasing evidence suggests that elements of the transition may be important in other processes, including metastasis and drug resistance in various different cancers. Methods Agilent 4 × 44 K whole human genome arrays and selected reaction monitoring mass spectrometry were used to investigate mRNA and protein expression in A2780 cisplatin sensitive and resistant cell lines. Invasion and migration were assessed using Boyden chamber assays. Gene knockdown of snail and slug was done using targeted siRNA. Clinical relevance of the EMT pathway was assessed in a cohort of primary ovarian tumours using data from Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. Results Morphological and phenotypic hallmarks of EMT were identified in the chemoresistant cells. Subsequent gene expression profiling revealed upregulation of EMT-related transcription factors including snail, slug, twist2 and zeb2. Proteomic analysis demonstrated up regulation of Snail and Slug as well as the mesenchymal marker Vimentin, and down regulation of E-cadherin, an epithelial marker. By reducing expression of snail and slug, the mesenchymal phenotype was largely reversed and cells were resensitized to cisplatin. Finally, gene expression data from primary tumours mirrored the finding that an EMT-like pathway is activated in resistant tumours relative to sensitive tumours, suggesting that the involvement of this transition may not be limited to in vitro drug effects. Conclusions This work strongly suggests that genes associated with EMT may play a significant role in cisplatin resistance in ovarian cancer, therefore potentially leading to the development of predictive biomarkers of drug response or novel therapeutic strategies for

Correlation between residual level of DNA double-strand breaks and the radiosensitivity of cancer cells

International Nuclear Information System (INIS)

Sun Jianxiang; Sun Weijian; Sui Jianli; Zhou Pingkun

2008-01-01

Objective: To understand the variation of the DNA double-strand break rejoining capacity among different cultured cancer cell lines and the primary cancer cells from brain cancer patients, and to explore the predictor of radiotherapy responses of cancers. Methods: DNA double-strand breaks (DSBs) were induced by 60 Co γ-irradiation. Pulsed-field gel electrophoresis was used to analyze the initial production and rejoining of DNA DSBs. Radiosensitivity was determined by in vitro assay of clonogenic-forming capacity. Results: A wide variation of radiosensitivity, e.g. the survival parameter of Do varied from 0.65 to 2.15 Gy, was displayed among the eight cell lines derived from different type of cancers. Although differential level of initial DNA DSBs induced by 20 Gy γ-rays was observed among various cell lines, it was not correlated with the radiosensitivity. The deficiency of DNA DSB rejoining in radiosensitive cell lines was shown either in the early rapid-rejoining phase (SX-10 cells) or in the late slow-rejoining phase (A2780 cells). A significant relationship was observed between the residual level of DNA DSBs measured at 2 h post-20 Gy irradiation and the cellular radiosensitivity (D 0 or SF 2 ). The kinetic curves of rejoining DNA DSBs in the primary human brain tumor cells indicated a variation on DSB rejoining capacity among different individual tumor. The residual level of DNA DSBs after 2 h of rejoining post 20 Gy irradiation in primary human brain tumor cells is compatible to the results obtained in vitro culture cancer cell lines. Conclusions: The residual level of DNA DSBs is correlated with radioresistance of cancer cells, and the residual DNA damage is a useful parameter in predicting the response of tumor tissue to radiotherapy. (authors)

Burden of Obesity on Pediatric Inpatients with Acute Asthma Exacerbation in the United States.

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Okubo, Yusuke; Nochioka, Kotaro; Hataya, Hiroshi; Sakakibara, Hiroshi; Terakawa, Toshiro; Testa, Marcia

Obesity and asthma are common health problems in the United States. The objective of this study was to evaluate the clinical and economic burdens of obesity on hospitalized children with acute asthma exacerbation in 2012. Hospital discharge records of patients aged 2 to 18 years with a diagnosis of asthma were obtained from the 2012 Kids' Inpatient Database, wherein the data were compiled by the Agency for Healthcare Research and Quality. The discharge records were weighted to estimate the number of hospitalizations because of asthma exacerbations in the United States. To classify whether the patient was obese or not, we used the International Classification of Diseases, Ninth Revision, Clinical Modification code 278.0x. We compared the odds of using noninvasive or invasive mechanical ventilation, mean total charges for inpatient service, and length of hospital stay between obese and nonobese patients. A total of 74,338 patient discharges were extracted. Of these, 3,494 discharges were excluded because of chronic medical conditions. Using discharge weight variables, we estimated a total of 100,157 hospitalizations with asthma exacerbations among children aged between 2 and 18 years in 2012. Obesity was significantly associated with higher odds of using mechanical ventilation (odds ratio 1.59, 95% CI 1.28-1.99), higher mean total hospital charges (adjusted difference: $1588, 95% CI $802-$2529), and longer mean length of hospital stay (0.24 days, 95% CI 0.17-0.32 days) compared with nonobesity. These findings suggest that obesity is a significant risk factor of severe asthma exacerbation that requires mechanical ventilation, and obesity is an economically complicating factor. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Quantification of human opiate receptor concentration and affinity using high and low specific activity ( sup 11 C)diprenorphine and positron emission tomography

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Sadzot, B.; Price, J.C.; Mayberg, H.S.; Douglass, K.H.; Dannals, R.F.; Lever, J.R.; Ravert, H.T.; Wilson, A.A.; Wagner, H.N. Jr.; Feldman, M.A. (Johns Hopkins Medical Institutions, Baltimore, MD (USA))

1991-03-01

(11C)Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) (11C)diprenorphine. Two subjects were studied a third time using high SA (11C)diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of (11C)diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of (11C)diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

[Anthraquinones from the roots of Knoxia valerianoides].

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Zhao, Feng; Wang, Sujuan; Wu, Xiuli; Yu, Yang; Yue, Zhenggang; Liu, Bo; Lin, Sheng; Zhu, Chenggen; Yang, Yongchun; Shi, Jiangong

2011-11-01

To investigate the chemical constituents of the roots of Knoxia valerianoides and their biological activities. The anthraquinones were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC. Structures of the isolates were identified by their physical-chemical properties and spectroscopic analysis including 2D NMR and MS. Antioxidant, anti-HIV, neuroprotective, and cytotoxic activities were screened by using cell-based models. Twenty-two constituents were isolated from an ethanolic extract of the roots of K. valerianoides. Their structures were identified as nordamnacanthal (1), ibericin (2), rubiadin (3), damnacanthol (4), 2-ethoxymethylknoxiavaledin (5), 3-hydroxymorindone (6), knoxiadin (7), 2-formyl knoxiavaledin (8), lucidin (9), xanthopurpurin (10), 1, 3-dihydroxy-2-methoxy-9, 10- anthraquinone (11), lucidin(-methyl ether (12), digiferruginol (13), 3-hydroxy-2-methyl-9,10-anthraquinone (14), rubiadin-1-methyl ether (15), 6-methoxylucidin (-ethyl ether (16), 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone (17), 1,3-dihydroxy-2-hydroxy methyl-6-methoxy-9,10-anthraquinone (18), 1,3,6-trihydroxy-2-methoxymethyl-9,10- anthraquinone (19), 3,6-dihydroxy-2- hydroxymethyl-9,10-anthraquinone (20), and 1,6-dihydroxy-2-methyl-9,10-anthra quinone (21). In the in vitro assays, at a concentration of 1 x 10(-5) mol x L(-1), no compounds were active against human cancer cell lines (HCT-8, Bel7402, BGC-823, A549, and A2780), deserum and glutamate induced PC12-syn cell damage, LPS induced NO production in macrophage, Fe2+-cystine induced rat liver microsomal lipid peroxidation, HIV-1 replication, and protein tyrosine phosphatase 1B (PTP1B). Compounds 9-21 were obtained from the roots of K. valerianoides for the first time.

Comparative study of the shear bond strength of composite resin bonded to enamel treated with acid etchant and erbium, chromium: Yttrium, scandium, gallium, garnet laser

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Adel Sulaiman Alagl

2016-01-01

Full Text Available Aim: The purpose of this investigation is in vitro comparison of the shear bond strength (SBS of composite resin bonded to enamel pretreated with an acid etchant against enamel etched with erbium, chromium: yttrium, scandium, gallium, garnet (Er, Cr:YSGG laser. Materials and Methods: Sixty premolars were sectioned mesiodistally and these 120 specimens were separated into two groups of 60 each (Groups A and B. In Group A (buccal surfaces, enamel surface was etched using 37% phosphoric acid for 15 s. In Group B (lingual surfaces, enamel was laser-etched at 2W for 10 s by Er, Cr:YSGG laser operational at 2780 nm with pulse duration of 140 μs and a frequency of 20 Hz. After application of bonding agent on all test samples, a transparent plastic cylinder of 1.5 mm × 3 mm was loaded with composite and bonded by light curing for 20 s. All the samples were subjected to SBS analysis using Instron Universal testing machine. Failure modes were observed under light microscope and grouped as adhesive, cohesive, and mixed. Failure mode distributions were compared using the Chi-square test. Results: SBS values obtained for acid-etched enamel were in the range of 7.12–28.36 megapascals (MPa and for laser-etched enamel were in the range of 6.23–23.35 MPa. Mean SBS for acid-etched enamel was 15.77 ± 4.38 MPa, which was considerably greater (P < 0.01 than laser-etched enamel 11.24 ± 3.76 MPa. The Chi-square test revealed that the groups showed no statistically significant differences in bond failure modes. Conclusions: We concluded that the mean SBS of composite with acid etching is significantly higher as compared to Er, Cr: YSGG (operated at 2W for 10 s laser-etched enamel.

Asteroid spin-rate studies using large sky-field surveys

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Chang, Chan-Kao; Lin, Hsing-Wen; Ip, Wing-Huen; Prince, Thomas A.; Kulkarni, Shrinivas R.; Levitan, David; Laher, Russ; Surace, Jason

2017-12-01

Eight campaigns to survey asteroid rotation periods have been carried out using the intermediate Palomar Transient Factory in the past 3 years. 2780 reliable rotation periods were obtained, from which we identified two new super-fast rotators (SFRs), (335433) 2005 UW163 and (40511) 1999 RE88, and 23 candidate SFRs. Along with other three known super-fast rotators, there are five known SFRs so far. Contrary to the case of rubble-pile asteroids (i.e., bounded aggregations by gravity only), an internal cohesion, ranging from 100 to 1000 Pa, is required to prevent these five SFRs from flying apart because of their super-fast rotations. This cohesion range is comparable with that of lunar regolith. However, some candidates of several kilometers in size require unusually high cohesion (i.e., a few thousands of Pa). Therefore, the confirmation of these kilometer-sized candidates can provide important information about asteroid interior structure. From the rotation periods we collected, we also found that the spin-rate limit of C-type asteroids, which has a lower bulk density, is lower than for S-type asteroids. This result is in agreement with the general picture of rubble-pile asteroids (i.e., lower bulk density, lower spin-rate limit). Moreover, the spin-rate distributions of asteroids of 3 5 rev/day, regardless of the location in the main belt. The YORP effect is indicated to be less efficient in altering asteroid spin rates from our results when compared with the flat distribution found by Pravec et al. (Icarus 197:497-504, 2008. doi: 10.1016/j.icarus.2008.05.012). We also found a significant number drop at f = 5 rev/day in the spin-rate distributions of asteroids of D < 3 km.

Hierarchical clustering of HPV genotype patterns in the ASCUS-LSIL triage study

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Wentzensen, Nicolas; Wilson, Lauren E.; Wheeler, Cosette M.; Carreon, Joseph D.; Gravitt, Patti E.; Schiffman, Mark; Castle, Philip E.

2010-01-01

Anogenital cancers are associated with about 13 carcinogenic HPV types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common which complicate the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the ASCUS-LSIL triage study using unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered using complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: Cluster 1 included all CIN3 histology with abnormal cytology; Cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion (HSIL) cytology; Cluster 3 included older women with normal or low grade histology/cytology and low viral load; Cluster 4 included younger women with low grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: Group 1 included only HPV16; Group 2 included nine carcinogenic types plus non-carcinogenic HPV53 and HPV66; and Group 3 included non-carcinogenic types plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and HSIL. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease using unsupervised hierarchical clustering can address complex genotype distributions on a population level. PMID:20959485

Photocytotoxic trans-diam(m)ine platinum(IV) diazido complexes more potent than their cis isomers.

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Farrer, Nicola J; Woods, Julie A; Munk, Vivienne P; Mackay, Fiona S; Sadler, Peter J

2010-02-15

The photocytotoxicity of a series of anticancer trans-dihydroxido [Pt(N(3))(2)(OH)(2)(NH(3))(X)] (X = alkyl or aryl amine) platinum(IV) diazido complexes has been examined, and the influence of cis-trans isomerism has been investigated. A series of photoactivatable Pt(IV)-azido complexes has been synthesized: The synthesis, characterization, and photocytotoxicity of six mixed-ligand ammine/amine Pt(IV) diazido complexes, cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))(X)] where X = propylamine (4c), butylamine (5c), or pentylamine (6c) and aromatic complexes where X = pyridine (7c), 2-methylpyridine (8c), or 3-methylpyridine (9c) are reported. Six all-trans isomers have also been studied where X = methylamine (2t), ethylamine (3t), 2-methylpyridine (8t), 4-methylpyridine (10t), 3-methylpyridine (9t), and 2-bromo-3-methylpyridine (11t). All of the complexes exhibit intense azide-to-Pt(IV) LMCT bands (ca. 290 nm for trans and ca. 260 nm for cis). When irradiated with UVA light (365 nm), the Pt(IV) complexes undergo photoreduction to Pt(II) species, as monitored by UV-vis spectroscopy. The trans isomers of complexes containing aliphatic or aromatic amines were more photocytotoxic than their cis isomers. One of the cis complexes (9c) was nonphotocytotoxic despite undergoing photoreduction. Substitution of NH(3) ligands by MeNH(2) or EtNH(2) results in more potent photocytotoxicity for the all-trans complexes. The complexes were all nontoxic toward human keratinocytes (HaCaT) and A2780 human ovarian cancer cells in the dark, apart from the 3-methylpyridine (9t), 2-bromo-3-methylpyridine (11t), and 4-methylpyridine (10t) derivatives.

The antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo

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Shi, Dayong; Li, Jing; Guo, Shuju; Su, Hua; Fan, Xiao

2009-05-01

To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (1), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (2), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethyl-pyrocatechol (3), 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxy-diphenylmethane (4), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (6) were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTT assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Bel7402 and HCT-8. Their inhibitory activity against protein tyrosine kinase (PTK) with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana (EELN) was evaluated on S180-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 μg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4%, respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.

Sports injuries and illnesses in the Sochi 2014 Olympic Winter Games.

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Soligard, Torbjørn; Steffen, Kathrin; Palmer-Green, Debbie; Aubry, Mark; Grant, Marie-Elaine; Meeuwisse, Willem; Mountjoy, Margo; Budgett, Richard; Engebretsen, Lars

2015-04-01

Systematic surveillance of injuries and illnesses is the foundation for developing preventive measures in sport. To analyse the injuries and illnesses that occurred during the XXII Olympic Winter Games, held in Sochi in 2014. We recorded the daily occurrence (or non-occurrence) of injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Sochi 2014 medical staff. NOC and Sochi 2014 medical staff reported 391 injuries and 249 illnesses among 2780 athletes from 88 NOCs, equalling incidences of 14 injuries and 8.9 illnesses per 100 athletes over an 18-day period of time. Altogether, 12% and 8% of the athletes incurred at least one injury or illness, respectively. The percentage of athletes injured was highest in aerial skiing, snowboard slopestyle, snowboard cross, slopestyle skiing, halfpipe skiing, moguls skiing, alpine skiing, and snowboard halfpipe. Thirty-nine per cent of the injuries were expected to prevent the athlete from participating in competition or training. Women suffered 50% more illnesses than men. The rate of illness was highest in skeleton, short track, curling, cross-country skiing, figure skating, bobsleigh and aerial skiing. A total of 159 illnesses (64%) affected the respiratory system, and the most common cause of illness was infection (n=145, 58%). Overall, 12% of the athletes incurred at least one injury during the games, and 8% an illness, which is similar to prior Olympic Games. The incidence of injuries and illnesses varied substantially between sports. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mismatch repair and treatment resistance in ovarian cancer

International Nuclear Information System (INIS)

Helleman, Jozien; Staveren, Iris L van; Dinjens, Winand NM; Kuijk, Patricia F van; Ritstier, Kirsten; Ewing, Patricia C; Burg, Maria EL van der; Stoter, Gerrit; Berns, Els MJJ

2006-01-01

The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation

Mismatch repair and treatment resistance in ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Helleman, Jozien; Staveren, Iris L van [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Dinjens, Winand NM [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Kuijk, Patricia F van; Ritstier, Kirsten [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Ewing, Patricia C [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Burg, Maria EL van der; Stoter, Gerrit [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Berns, Els MJJ [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Erasmus MC, Department of Medical Oncology, Josephine Nefkens Institute, Room Be424, P.O. Box 1738, 3000 DR (Netherlands)

2006-07-31

The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

Mismatch repair and treatment resistance in ovarian cancer

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van der Burg Maria EL

2006-07-01

Full Text Available Abstract Background The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. Methods We determined, microsatellite instability (MSI as a marker for MMR inactivation (analysis of BAT25 and BAT26, MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR in 75 ovarian carcinomas and eight ovarian cancer cell lines Results MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation, SKOV3 (no MLH1 mRNA expression and 2774 (no altered expression of MMR genes. Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response. The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. Conclusion No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src.

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Mian M K Shahzad

Full Text Available The goal of this study was to investigate the anti-cancer effects of Trans10,cis12 conjugated linoleic acid (t10,c12 CLA. MTT assays and QCM™ chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting were used to determine the expression of specific factors. RNA sequencing was conducted using the Illumina platform and apoptosis was measured using a flow cytometry assay. t10,c12 CLA (IC50, 7 μM inhibited proliferation of ovarian cancer cell lines SKOV-3 and A2780. c9,t11 CLA did not attenuate the proliferation of these cells. Transcription of 165 genes was significantly repressed and 28 genes were elevated. Genes related to ER stress, ATF4, CHOP, and GADD34 were overexpressed whereas EDEM2 and Hsp90, genes required for proteasomal degradation of misfolded proteins, were downregulated upon treatment. While apoptosis was not detected, t10,c12 CLA treatment led to 9-fold increase in autophagolysosomes and higher levels of LC3-II. G1 cell cycle arrest in treated cells was correlated with phosphorylation of GSK3β and loss of β-catenin. microRNA miR184 and miR215 were upregulated. miR184 likely contributed to G1 arrest by downregulating E2F1. miR215 upregulation was correlated with increased expression of p27/Kip-1. t10,c12 CLA-mediated inhibition of invasion and migration correlated with decreased expression of PTP1b and decreased Src activation by inhibiting phosphorylation at Tyr416. Due to its ability to inhibit proliferation and migration, t10,c12 CLA should be considered for treatment of ovarian cancer.

Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src.

Science.gov (United States)

Shahzad, Mian M K; Felder, Mildred; Ludwig, Kai; Van Galder, Hannah R; Anderson, Matthew L; Kim, Jong; Cook, Mark E; Kapur, Arvinder K; Patankar, Manish S

2018-01-01

The goal of this study was to investigate the anti-cancer effects of Trans10,cis12 conjugated linoleic acid (t10,c12 CLA). MTT assays and QCM™ chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting were used to determine the expression of specific factors. RNA sequencing was conducted using the Illumina platform and apoptosis was measured using a flow cytometry assay. t10,c12 CLA (IC50, 7 μM) inhibited proliferation of ovarian cancer cell lines SKOV-3 and A2780. c9,t11 CLA did not attenuate the proliferation of these cells. Transcription of 165 genes was significantly repressed and 28 genes were elevated. Genes related to ER stress, ATF4, CHOP, and GADD34 were overexpressed whereas EDEM2 and Hsp90, genes required for proteasomal degradation of misfolded proteins, were downregulated upon treatment. While apoptosis was not detected, t10,c12 CLA treatment led to 9-fold increase in autophagolysosomes and higher levels of LC3-II. G1 cell cycle arrest in treated cells was correlated with phosphorylation of GSK3β and loss of β-catenin. microRNA miR184 and miR215 were upregulated. miR184 likely contributed to G1 arrest by downregulating E2F1. miR215 upregulation was correlated with increased expression of p27/Kip-1. t10,c12 CLA-mediated inhibition of invasion and migration correlated with decreased expression of PTP1b and decreased Src activation by inhibiting phosphorylation at Tyr416. Due to its ability to inhibit proliferation and migration, t10,c12 CLA should be considered for treatment of ovarian cancer.

Urban-rural and geographic differences in overweight and obesity in four sub-Saharan African adult populations: a multi-country cross-sectional study.

Science.gov (United States)

Ajayi, IkeOluwapo O; Adebamowo, Clement; Adami, Hans-Olov; Dalal, Shona; Diamond, Megan B; Bajunirwe, Francis; Guwatudde, David; Njelekela, Marina; Nankya-Mutyoba, Joan; Chiwanga, Faraja S; Volmink, Jimmy; Kalyesubula, Robert; Laurence, Carien; Reid, Todd G; Dockery, Douglas; Hemenway, David; Spiegelman, Donna; Holmes, Michelle D

2016-10-28

Overweight and obesity are on the rise in developing countries including sub-Saharan Africa. We undertook a four-country survey to show the collective burden of these health conditions as they occur currently in sub-Saharan Africa and to determine the differences between urban and rural populations and other socio-economic factors. Participants were nurses in two hospitals in Nigeria (200), school teachers in South Africa (489) and Tanzania (229), and village residents in one peri-urban (297) and one rural location in Uganda (200) who completed a standardised questionnaire. Their height and weight were measured and body mass index calculated. Factor analysis procedure (Principal component) was used to generate a wealth index. Univariate and multivariate analyses with binary logistic regression models were conducted to examine the associations between potential correlates and the prevalence of overweight and obesity with 95 % confidence intervals. The prevalence of overweight and obese (combined) was 46 %, 48 %, 68 %, 75 % and 85 % in rural Uganda, peri-urban Uganda, Nigeria, Tanzania and South Africa (SA), respectively. Rural Uganda, Peri- urban Uganda, Nigeria, Tanzania and SA had obesity prevalence of 10 %, 14 %, 31 %, 40 % and 54 %, respectively (p obesity, 414 (34 %). Female sex was a predictor of overweight and obesity (combined) in peri-urban Uganda [AOR = 8.01; 95 % CI: 4.02, 15.96) and obesity in rural Uganda [AOR = 11.22; 95%CI: 2.27, 55.40), peri-urban Uganda [AOR = 27.80; 95 % CI: 7.13, 108.41) and SA [AOR = 2.17; 95 % CI: 1.19, 4.00). Increasing age was a predictor of BMI > =25 kg/m 2 in Nigeria [Age > =45 - AOR = 9.11; 95 % CI: 1.72, 48.16] and SA [AOR = 6.22; 95 % CI: 2.75, 14.07], while marital status was predictor of BMI > =25 kg/m 2 only in peri-urban Uganda. [Married - AOR = 4.49; 95 % CI: 1.74, 11.57]. Those in Nigeria [AOR = 2.56; 95 % CI: 1.45, 4.53], SA [AOR = 4.97; 95 % CI: 3

Acceptance of and attitudes towards human papillomavirus vaccination in Japanese mothers of adolescent girls.

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Hanley, Sharon J B; Yoshioka, Eiji; Ito, Yoshiya; Konno, Ryo; Hayashi, Yuri; Kishi, Reiko; Sakuragi, Noriaki

2012-08-24

To better understand how to achieve high uptake rates of human papillomavirus (HPV) vaccination in Japan, we investigated acceptance of and attitudes towards HPV vaccination in 2192 mothers of girls aged 11-14 yrs. A school-based survey was conducted in five elementary and fourteen junior high schools in Sapporo, Japan. Responses from 862 participants were analyzed. Ninety-three percent of mothers would accept the vaccine for their daughter if free, but only 1.5% was willing to pay the minimum recommended price of ¥ 40,000. Vaccine acceptance was higher in mothers who had heard of HPV vaccine (adjusted odds ratio, aOR=2.58, confidence interval, CI=1.47-4.53), and who believed susceptibility to (aOR=2.30, CI=1.34-3.92) and severity of (aOR=3.73, CI=1.41-9.88) HPV to be high. Recommendations from a doctor (aOR=12.60, CI=7.06-21.48) and local health board (aOR=27.80, CI=13.88-55.86) were also positively associated with increased HPV vaccine acceptance. Concerns about side effects of both the HPV vaccine (aOR=0.03, CI=0.01-0.08) and routine childhood vaccines in general (aOR=0.11, CI=0.02-0.78) emerged as barriers to vaccination. Not participating in routine cervical screening also emerged as a deterrent (aOR=0.49, CI=0.27-0.91). While most mothers (66.8%) agreed that 10-14 yr was an appropriate age for vaccination, a further 30.6% believed >15 yr to be more appropriate. In conclusion, attitudes of Japanese mothers toward HPV vaccination are encouraging. While lower vaccine acceptance in mothers who do not undergo regular cervical screening needs further investigation, this study indicates that high uptake may be possible in a publically funded HPV vaccination program if physicians actively address safety concerns and justify why the vaccine is needed at a particular age. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ethnicity and skin autofluorescence-based risk-engines for cardiovascular disease and diabetes mellitus.

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Muhammad Saeed Ahmad

Full Text Available Skin auto fluorescence (SAF is used as a proxy for the accumulation of advanced glycation end products (AGEs and has been proposed to stratify patients into cardiovascular disease (CVD and diabetes mellitus (DM risk groups. This study evaluates the effects of seven different ethnicities (Arab, Central-East African, Eastern Mediterranean, European, North African, South Asian and Southeast Asian and gender on SAF as well as validating SAF assessment as a risk estimation tool for CVD and DM in an Arabian cohort. SAF data from self-reported healthy 2,780 individuals, collated from three independent studies, has been linear modelled using age and gender as a covariate. A cross-study harmonized effect size (Cohens'd is provided for each ethnicity. Furthermore, new data has been collected from a clinically well-defined patient group of 235 individuals, to evaluate SAF as a clinical tool for DM and CVD-risk estimation in an Arab cohort. In an Arab population, SAF-based CVD and/or DM risk-estimation can be improved by referencing to ethnicity and gender-specific SAF values. Highest SAF values were observed for the North African population, followed by East Mediterranean, Arab, South Asian and European populations. The South Asian population had a slightly steeper slope in SAF values with age compared to other ethnic groups. All ethnic groups except Europeans showed a significant gender effect. When compared with a European group, effect size was highest for Eastern Mediterranean group and lowest for South Asian group. The Central-East African and Southeast Asian ethnicity matched closest to the Arab and Eastern Mediterranean ethnicities, respectively. Ethnic and gender-specific data improves performance in SAF-based CVD and DM risk estimation. The provided harmonized effect size allows a direct comparison of SAF in different ethnicities. For the first time, gender differences in SAF are described for North African and East Mediterranean populations.

Physicochemical Properties, Antioxidant and Cytotoxic Activities of Crude Extracts and Fractions from Phyllanthus amarus

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Van Tang Nguyen

2017-06-01

Full Text Available Background: Phyllanthus amarus (P. amarus has been used as a medicinal plant for the prevention and treatment of chronic ailments such as diabetes, hepatitis, and cancer. Methods: The physicochemical properties, antioxidant and cytotoxic activities of crude extracts and fractions from P. amarus were determined using spectrophotometric method. Results: The P. amarus methanol (PAM extract had lower levels of residual moisture (7.40% and water activity (0.24 and higher contents of saponins, phenolics, flavonoids, and proanthocyanidins (1657.86 mg escin equivalents, 250.45 mg gallic acid equivalents, 274.73 mg rutin equivalents and 61.22 mg catechin equivalents per g dried extract, respectively than those of the P. amarus water (PAW extract. The antioxidant activity of PAM extract was significantly higher (p < 0.05 than that of the PAW extract, PAM fractions, and phyllanthin (known as a major compound in the P. amarus. Higher cytotoxic activity of PAM extract based on MTT assay on different cell lines including MiaPaCa-2 (pancreas, HT29 (colon, A2780 (ovarian, H460 (lung, A431 (skin, Du145 (prostate, BE2-C (neuroblastoma, MCF-7 (breast, MCF-10A (normal breast, and U87, SJ-G2, SMA (glioblastoma was observed in comparison to the PAW extract and PAM fractions. The cytotoxic potential of the PAW extract (200 μg/mL, based on the CCK-8 assay on a pancreatic cancer cell line (MiaCaPa2 was significantly lower (p < 0.05 than those of gemcitabine (50 nM and a saponin-enriched extract from quillajia bark at 200 μg/mL (a commercial product, but was significantly higher than that of phyllanthin at 2 μg/mL. Conclusions: The results achieved from this study reveal that the PA extracts are a potential source for the development of natural antioxidant products and/or novel anticancer drugs.

IL6 induces TAM resistance via kinase-specific phosphorylation of ERα in OVCA cells.

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Wang, Yue; Niu, Xiu Long; Guo, Xiao Qin; Yang, Jing; Li, Ling; Qu, Ye; Xiu Hu, Cun; Mao, Li Qun; Wang, Dan

2015-06-01

About 40-60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we demonstrate that both exogenous (a relatively short period of treatment with recombinant IL6) and endogenous IL6 (generated as a result of transfection with a plasmid encoding sense IL6) increases expression of pERα-Ser118 and pERα-Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6 expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid encoding antisense IL6) reduces expression of pERα-Ser118 and pERα-Ser167, indicating that IL6-induced TAM resistance may also be associated with increased expression of pERα-Ser118 and pERα-Ser167 in OVCA cells. Results of further investigation indicate that IL6 phosphorylates ERα at Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3 kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA cells may also contribute to the refractoriness of these cells to TAM via the crosstalk between ER and IL6-mediated intracellular signal transduction cascades. Overexpression of IL6 not only plays an important role in OVCA progression but also promotes TAM resistance. Our results indicate that TAM-IL6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2015 Society for Endocrinology.

Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

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Bree, Chris van; Kreder, Natasja Castro; Loves, Willem J.P.; Franken, Nicolaas A.P.; Peters, Godefridus J.; Haveman, Jaap

2002-01-01

Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5-fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000 were determined by clonogenic assay. Bivariate flowcytometry was performed to study cell cycle changes. Results: In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level. This was accompanied by a 10-fold decrease in dCK activity which resulted in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50-100 μM dFdC) induced radioenhancement in the dFdC-resistant cell lines similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in the parental lines. An early S-phase arrest was found in all cell lines after dFdC treatment where radioenhancement was achieved. Conclusions: In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. No cross-resistance was observed to other anti-tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing radiation was not altered in two different dFdC-resistant cell lines. Resistance to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation

Carotid intima-media thickness and plasma fibrinogen among subjects with metabolic syndrome: Isfahan cohort study

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Zahra Bayanfar

2014-09-01

Full Text Available BACKGROUND: The role of plasma fibrinogen, a key regulator of inflammation processes and increased carotid intima-media thickness (cIMT to predict metabolic syndrome (MetS is currently under investigation. We assessed differences in the indicators of cIMT and also plasma fibrinogen level between MetS and non-MetS subjects. We also assessed the role of these two parameters for independently relationship with MetS state. METHODS: The subjects in this cross-sectional survey were population-based samples of 93 men and women aged ≥ 35 years and over who were selected from the Isfahan cohort study, Isfahan, Iran. Fibrinogen was measured by the clotting assay of Clauss. Ultrasound studies of the carotid artery were performed to measure cIMT. MetS defined based on the National Cholesterol Education Program’s Adult Treatment Panel III. RESULTS: The mean level of plasma fibrinogen was not different in the two groups with and without MetS (240.10 ± 27.80 vs. 242.56 ± 35.82, P = 0.714, but the mean of cIMT was considerably higher in MetS group than in non-MetS group (0.85 ± 0.06 mm vs. 0.66 ± 0.09 mm, P < 0.001. Using a multivariable logistic regression model, high cIMT could effectively predict MetS state with the presence of different components of MetS (odds ratio = 17.544, 95% confidence interval: 2.151-142.860, P = 0.008. The optimal cutoff point of cIMT for discriminating these two clinical states was 0.6 mm yielding a sensitivity of 61.5% and a specificity of 59.6%. CONCLUSION: Individuals with MetS demonstrated increased cIMT values compared with those without MetS. However, high plasma fibrinogen level may not be associated with MetS state.   Keywords: Metabolic Syndrome, Carotid Intima-Media Thickness, Fibrinogen, Prediction 

Thoracic cavity segmentation algorithm using multiorgan extraction and surface fitting in volumetric CT

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Bae, JangPyo [Interdisciplinary Program, Bioengineering Major, Graduate School, Seoul National University, Seoul 110-744, South Korea and Department of Radiology, University of Ulsan College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Kim, Namkug, E-mail: namkugkim@gmail.com; Lee, Sang Min; Seo, Joon Beom [Department of Radiology, University of Ulsan College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Kim, Hee Chan [Department of Biomedical Engineering, College of Medicine and Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-744 (Korea, Republic of)

2014-04-15

Purpose: To develop and validate a semiautomatic segmentation method for thoracic cavity volumetry and mediastinum fat quantification of patients with chronic obstructive pulmonary disease. Methods: The thoracic cavity region was separated by segmenting multiorgans, namely, the rib, lung, heart, and diaphragm. To encompass various lung disease-induced variations, the inner thoracic wall and diaphragm were modeled by using a three-dimensional surface-fitting method. To improve the accuracy of the diaphragm surface model, the heart and its surrounding tissue were segmented by a two-stage level set method using a shape prior. To assess the accuracy of the proposed algorithm, the algorithm results of 50 patients were compared to the manual segmentation results of two experts with more than 5 years of experience (these manual results were confirmed by an expert thoracic radiologist). The proposed method was also compared to three state-of-the-art segmentation methods. The metrics used to evaluate segmentation accuracy were volumetric overlap ratio (VOR), false positive ratio on VOR (FPRV), false negative ratio on VOR (FNRV), average symmetric absolute surface distance (ASASD), average symmetric squared surface distance (ASSSD), and maximum symmetric surface distance (MSSD). Results: In terms of thoracic cavity volumetry, the mean ± SD VOR, FPRV, and FNRV of the proposed method were (98.17 ± 0.84)%, (0.49 ± 0.23)%, and (1.34 ± 0.83)%, respectively. The ASASD, ASSSD, and MSSD for the thoracic wall were 0.28 ± 0.12, 1.28 ± 0.53, and 23.91 ± 7.64 mm, respectively. The ASASD, ASSSD, and MSSD for the diaphragm surface were 1.73 ± 0.91, 3.92 ± 1.68, and 27.80 ± 10.63 mm, respectively. The proposed method performed significantly better than the other three methods in terms of VOR, ASASD, and ASSSD. Conclusions: The proposed semiautomatic thoracic cavity segmentation method, which extracts multiple organs (namely, the rib, thoracic wall, diaphragm, and heart

Tunable microwave absorbing nano-material for X-band applications

International Nuclear Information System (INIS)

Sadiq, Imran; Naseem, Shahzad; Ashiq, Muhammad Naeem; Khan, M.A.; Niaz, Shanawer; Rana, M.U.

2016-01-01

The effect of rare earth elements substitution in Sr_1_._9_6RE_0_._0_4Co_2Fe_2_7_._8_0Mn_0_._2O_4_6 (RE=Ce, Gd, Nd, La and Sm) X-type hexagonal ferrites prepared by using sol gel autocombustion method was studied. The XRD and FTIR analysis show the single phase of the prepared material. The lattice constants a (Å) and c (Å) varies with the additives. The particle size measured by Scherer formula for all the samples varies in the range of 54–100 nm and confirmed by the TEM analysis. The average grain size measured by SEM analysis lies in the range of 0.672–1.01 µm for all the samples. The Gd-substituted ferrite has higher value of coercivity (526.06 G) among all the samples which could be a good material for longitudinal recording media. The results also indicate that the Gd-substituted sample has maximum reflection loss of −25.2 dB at 11.878 GHz, can exhibit the best microwave absorption properties among all the substituted samples. Furthermore, the minimum value of reflection loss shifts towards the lower and higher frequencies with the substitution of rare earth elements which confirms that the microwave absorption properties can be tuned with the substitution of rare earth elements in pure ferrites. The peak value of attenuation constant at higher frequency agrees well the reflection loss data. - Highlights: • A series of X-type hexagonal ferrites were prepared by sol–gel method. • The XRD analysis showed that the X-type hexagonal structure. • The c/a ratio of these samples falls in the range of X-type hexagonal ferrites. • FTIR spectra confirms single hexagonal phase. • The magnetic properties vary with the substitution of rare earth elements. • The Gd-doped sample exhibits maximum absorption properties and coercivity.

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

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Kumar, Raj [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Siril, Prem Felix, E-mail: prem@iitmandi.ac.in [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Javid, Farideh [School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH (United Kingdom)

2016-12-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Climate in the Western Cordillera of the Central Andes over the last 4300 years

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Engel, Zbyněk; Skrzypek, Grzegorz; Chuman, Tomáš; Šefrna, Luděk; Mihaljevič, Martin

2014-09-01

The Distichia peat core obtained in the Carhuasanta valley near Nevado Mismi, Cordillera Chila, provides information on climatic and environmental conditions over the last ˜4300 years. The relative changes in the stable carbon isotope composition of plant remains preserved in the core reflect major temperature fluctuations in the Western Cordillera of the southern Peruvian Andes. These temperature variations can be additionally linked with the changes in precipitation patterns by analysing C% and C/N ratio in the core. Relatively warm and moist conditions prevailed from 4280 to 3040 cal. yrs BP (BC 2330-1090) with a short colder dry episode around 3850 cal. yrs BP (BC 1900). The most prominent climate changes recorded in the peat occurred between 3040 and 2750 cal. yrs BP (BC 1090-800) when the initial warming turned to a rapid cooling to temperatures at least 2 °C lower than the mean for the Late Holocene. Initially drier conditions within this event turned to a short wet phase after 2780 cal. yrs BP (BC 830) when the temperature increased again. This event coincides with significant changes in peat and ice core records in the Central Andes matching the timing of the global climate event around 2.8 cal. ka BP. Climatic conditions in the study area became relatively dry and stable after the event for about 800 years. Highly variable temperatures and humidity prevailed during the last 2000 years when an extended warm and relatively humid period occurred between 640 and 155 cal. yrs BP (AD 1310-1795) followed by predominantly colder and drier conditions. The established δ13C peat record represents the first continuous proxy for the temperature in the southern Peruvian Andes dated by the AMS 14C. Distichia peat is wide spread in the Andes and the proposed approach can be applied elsewhere in high altitudes, where no other traditional climate proxies are available.

Human management and landscape changes at Palaikastro (Eastern Crete) from the Late Neolithic to the Early Minoan period

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Cañellas-Boltà, N.; Riera-Mora, S.; Orengo, H. A.; Livarda, A.; Knappett, C.

2018-03-01

On the east Mediterranean island of Crete, a hierarchical society centred on large palatial complexes emerges during the Bronze Age. The economic basis for this significant social change has long been debated, particularly concerning the role of olive cultivation in the island's agricultural system. With the aim of studying vegetation changes and human management to understand the landscape history from Late Neolithic to Bronze Age, two palaeoenvironmental records have been studied at Kouremenos marsh, near the site of Palaikastro (Eastern Crete). Pollen, NPP and charcoal particles analyses evidenced seven phases of landscape change, resulting from different agricultural and pastoral practices and the use of fire probably to manage vegetation. Moreover, the Kouremenos records show the importance of the olive tree in the area. They reflect a clear trend for its increasing use and exploitation from 3600 cal yr BC (Final Neolithic) to the Early Minoan period, that is coeval with an opening of the landscape. The increase of Olea pollen was due to the expansion of the tree and its management using pruning and mechanical cleaning. The onset of olive expansion at c. 3600 cal yr BC places Crete among the first locales in the eastern Mediterranean in the management of this tree. Between c. 2780 and 2525 cal yr BC the landscape was largely occupied by olive and grasslands, coinciding with an increase in grazing practices. The high Olea pollen percentages (40-45%) suggest an intensive and large-scale exploitation of the olive tree. The results suggest that a complex and organized landscape with complementary land uses and activities was already in place since the Final Neolithic. The notable expansion of olive trees suggests the relevance of olive exploitation in the socio-economic development of Minoan towns of eastern Crete. Other crops, such as cereals and vine, and activities such as grazing have also played an important role in the configuration of the past landscape.

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

International Nuclear Information System (INIS)

Kumar, Raj; Siril, Prem Felix; Javid, Farideh

2016-01-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

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Chung Jae

2009-06-01

Full Text Available Abstract Background Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition. Methods To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis. Results Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99 between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells. Conclusion Selective epigenetic disruption of distinct biological

QTL mapping of downy and powdery mildew resistances in PI 197088 cucumber with genotyping-by-sequencing in RIL population.

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Wang, Yuhui; VandenLangenberg, Kyle; Wen, Changlong; Wehner, Todd C; Weng, Yiqun

2018-03-01

Host resistances in PI 197088 cucumber to downy and powdery mildew pathogens are conferred by 11 (3 with major effect) and 4 (1 major effect) QTL, respectively, and three of which are co-localized. The downy mildew (DM) and powdery mildew (PM) are the two most important foliar diseases of cucurbit crops worldwide. The cucumber accession PI 197088 exhibits high-level resistances to both pathogens. Here, we reported QTL mapping results for DM and PM resistances with 148 recombinant inbred lines from a cross between PI 197088 and the susceptible line 'Coolgreen'. Phenotypic data on responses to natural DM and PM infection were collected in multi-year and multi-location replicated field trials. A high-density genetic map with 2780 single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing and 55 microsatellite markers was developed, which revealed genomic regions with segregation distortion and mis-assemblies in the '9930' cucumber draft genome. QTL analysis identified 11 and 4 QTL for DM and PM resistances accounting for more than 73.5 and 63.0% total phenotypic variance, respectively. Among the 11 DM resistance QTL, dm5.1, dm5.2, and dm5.3 were major-effect contributing QTL, whereas dm1.1, dm2.1, and dm6.2 conferred susceptibility. Of the 4 QTL for PM resistance, pm5.1 was the major-effect QTL explaining 32.4% phenotypic variance and the minor-effect QTL pm6.1 contributed to disease susceptibility. Three PM QTL, pm2.1, pm5.1, and pm6.1, were co-localized with DM QTL dm2.1, dm5.2, and dm6.1, respectively, which was consistent with the observed linkage of PM and DM resistances in PI 197088. The genetic architecture of DM resistance in PI 197088 and another resistant line WI7120 (PI 330628) was compared, and the potential of using PI 197088 in cucumber breeding for downy and powdery mildew resistances is discussed.

Associations Between Exposure to and Expression of Negative Opinions About Human Papillomavirus Vaccines on Social Media: An Observational Study.

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Dunn, Adam G; Leask, Julie; Zhou, Xujuan; Mandl, Kenneth D; Coiera, Enrico

2015-06-10

Groups and individuals that seek to negatively influence public opinion about the safety and value of vaccination are active in online and social media and may influence decision making within some communities. We sought to measure whether exposure to negative opinions about human papillomavirus (HPV) vaccines in Twitter communities is associated with the subsequent expression of negative opinions by explicitly measuring potential information exposure over the social structure of Twitter communities. We hypothesized that prior exposure to opinions rejecting the safety or value of HPV vaccines would be associated with an increased risk of posting similar opinions and tested this hypothesis by analyzing temporal sequences of messages posted on Twitter (tweets). The study design was a retrospective analysis of tweets related to HPV vaccines and the social connections between users. Between October 2013 and April 2014, we collected 83,551 English-language tweets that included terms related to HPV vaccines and the 957,865 social connections among 30,621 users posting or reposting the tweets. Tweets were classified as expressing negative or neutral/positive opinions using a machine learning classifier previously trained on a manually labeled sample. During the 6-month period, 25.13% (20,994/83,551) of tweets were classified as negative; among the 30,621 users that tweeted about HPV vaccines, 9046 (29.54%) were exposed to a majority of negative tweets. The likelihood of a user posting a negative tweet after exposure to a majority of negative opinions was 37.78% (2780/7361) compared to 10.92% (1234/11,296) for users who were exposed to a majority of positive and neutral tweets corresponding to a relative risk of 3.46 (95% CI 3.25-3.67, Prelation to HPV vaccines. We found that among users that tweeted about HPV vaccines, those who were more often exposed to negative opinions were more likely to subsequently post negative opinions. Although this research may be useful for

High seroprevalance of Neospora caninum in dogs in Victoria, Australia, compared to 20 years ago

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Sarah Sloan

2017-10-01

Full Text Available Abstract Background Canids are definitive hosts of the apicomplexan parasite Neospora caninum, the leading cause of abortion in cattle worldwide. For horizontal transmission from canids to occur, oocysts of N. caninum must be shed by the definitive host into the environment of susceptible intermediate hosts such as cattle. The purpose of this study was to determine the prevalence of N. caninum in canids in Victoria, Australia’s leading dairy producing state. Results Neospora-like oocysts were observed in 8% (18/234 of faecal samples from wild dogs, domestic dogs and red foxes from Victoria, Australia. However, none tested positive for N. caninum DNA using a quantitative PCR. In a separate sample population, blood sera from 483 domestic dogs were tested for anti-N. caninum antibodies using competitive ELISA. A subset of cELISA samples were re-tested using indirect fluorescence antibody test (IFAT. A seroprevalence of 29.8% (144/483; 95% CI: 11.7–47.8% was calculated when using cELISA; whereas it was 32.9% (27/80; 95% CI: 15.8–51.8% using IFAT. Potential risk factors were evaluated using univariable analyses and then assessed in separate multivariable models. Using ‘aged’ dogs as a reference, the seroprevalence of ‘adolescent’ and ‘adult’ dogs was 88% (P = 0.05 and 91% (P = 0.08, respectively, indicating seroprevalence increases with age. There was a 19% higher likelihood of infection in rural locations (P = 0.10 relative to urban areas. Jack Russell Terriers had a 22% higher risk of a cELISA-positive result (P = 0.05 regardless of geographical location, age or sex. Conclusion These results demonstrate that exposure to N. caninum in domestic dogs is widespread in Victoria, although faecal oocyst shedding is infrequent. Our results indicate increased N. caninum seroprevalance status in dogs over the past two decades. The results imply that dogs get either exposed to the infected meat more frequently or that vertical dam to

Anticancer Efficacy of Polyphenols and Their Combinations

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Aleksandra Niedzwiecki

2016-09-01

Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

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Ye, Shuangmei; Chen, Yin; You, Lanying; Zhang, Yiqun; Xu, Gang; Zhou, Jianfeng; Ma, Ding; Wang, Shixuan; Hao, Xing; Zhou, Ting; Wu, Mingfu; Wei, Juncheng; Wang, Yongjun; Zhou, Li; Jiang, Xuefeng; Ji, Li

2010-01-01

Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro. Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKT Ser473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining. Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not

An antitubulin agent BCFMT inhibits proliferation of cancer cells and induces cell death by inhibiting microtubule dynamics.

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Ankit Rai

Full Text Available Using cell based screening assay, we identified a novel anti-tubulin agent (Z-5-((5-(4-bromo-3-chlorophenylfuran-2-ylmethylene-2-thioxothiazolidin-4-one (BCFMT that inhibited proliferation of human cervical carcinoma (HeLa (IC(50, 7.2 ± 1.8 µM, human breast adenocarcinoma (MCF-7 (IC(50, 10.0 ± 0.5 µM, highly metastatic breast adenocarcinoma (MDA-MB-231 (IC(50, 6.0 ± 1 µM, cisplatin-resistant human ovarian carcinoma (A2780-cis (IC(50, 5.8 ± 0.3 µM and multi-drug resistant mouse mammary tumor (EMT6/AR1 (IC(50, 6.5 ± 1 µM cells. Using several complimentary strategies, BCFMT was found to inhibit cancer cell proliferation at G2/M phase of the cell cycle apparently by targeting microtubules. In addition, BCFMT strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory concentration (10 µM, BCFMT reduced the rates of growing and shortening phases of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased the time microtubules spent in the pause (neither growing nor shortening detectably state by 135% and reduced the dynamicity (dimer exchange per unit time of microtubules by 70%. In vitro, BCFMT bound to tubulin with a dissociation constant of 8.3 ± 1.8 µM, inhibited tubulin assembly and suppressed GTPase activity of microtubules. BCFMT competitively inhibited the binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration (K(i of 5.2 ± 1.5 µM suggesting that it binds to tubulin at the vinblastine site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules, perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and Mad2 at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear accumulation of p53 and its downstream p21, which consequently activated apoptosis in these cells. The results suggested that BCFMT inhibits proliferation of several types of cancer cells including drug

Reduction of costs for anemia-management drugs associated with the use of ferric citrate

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Thomas A

2014-05-01

Full Text Available Anila Thomas,1 Leif E Peterson2 1Clinical Pharmacy Services, Houston Methodist Hospital, Houston, TX, USA; 2Center for Biostatistics, Houston Methodist Research Institute, Houston, TX, USA Background: Ferric citrate is a novel phosphate binder which has the potential to reduce usage of erythropoietin-stimulating agents (ESAs and intravenous (IV iron used for anemia management during hemodialysis (HD among patients with end-stage renal disease (ESRD. Currently, the potential health care cost savings on a national scale due to the use of ferric citrate in ESRD are undetermined. Methods: Per-patient-per-year costs of ESAs (Epogen® and Aranesp® [Amgen Inc., CA, USA] and IV iron (Venofer® [American Regent, Inc., NY, USA] and Ferrlecit® [Sanofi US, Bridgewater, NJ, USA] were based on RED BOOK™ (Truven Health Analytics New York, NY, USA costs combined with the Centers for Medicare and Medicaid Services (CMS base rate and actual usage in 2011 for the four drugs. The annual number of outpatients undergoing HD in the US was based on frequencies reported by the USRDS (United States Renal Data System. Monte Carlo uncertainty analysis was performed to determine total annual costs and cost reduction based on ferric citrate usage. Results: Total annual cost of ESAs and IV iron for anemia management in ESRD determined by Monte Carlo analysis assuming CMS base rate value was 5.127 (3.664–6.260 billion USD. For actual utilization in 2011, total annual cost of ESAs and IV iron was 3.981 (2.780–4.930 billion USD. If ferric citrate usage reduced ESA utilization by 20% and IV iron by 40%, then total cost would be reduced by 21.2% to 4.038 (2.868–4.914 billion USD for the CMS base rate, and by 21.8% to 3.111 (2.148–3.845 billion USD, based on 2011 actual utilization. Conclusion: It is likely that US health care costs for anemia-management drugs associated with ESRD among HD patients can be reduced by using ferric citrate as a phosphate binder. Keywords

Intimate partner violence and HIV infection among married Indian women.

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Silverman, Jay G; Decker, Michele R; Saggurti, Niranjan; Balaiah, Donta; Raj, Anita

2008-08-13

Despite reductions in prevalence of human immunodeficiency virus (HIV) infection among the general population of India, women account for a rising percentage of all HIV cases with husbands' risk behavior described as the major source of women's infection. Intimate partner violence (IPV) has been described as being associated with heterosexual transmission of HIV to women in India and elsewhere. To assess the relationship between experiencing IPV and the occurrence of HIV infection in a nationally representative sample of married Indian women tested for HIV. The Indian National Family Health Survey 3 was conducted across all Indian states in 2005 through 2006. The nationally representative sample included 124,385 married women; analyses conducted in 2007 and 2008 were limited to 28,139 married women who provided IPV data and HIV test results via systematic selection into respective subsamples. Prevalence estimates of lifetime IPV and HIV infection were calculated and demographic differences assessed. Intimate partner violence was conceptualized as physical violence with or without sexual violence and then was further categorized as physical violence only vs physical and sexual violence. Regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for HIV infection among Indian women based on experiences of IPV after adjusting for demographics and women's HIV risk behaviors. One-third of married Indian women (35.49%) reported experiencing physical IPV with or without sexual violence from their husbands; 7.68% reported both physical and sexual IPV, and 27.80% reported experiencing physical IPV in the absence of sexual violence. Approximately 1 in 450 women (0.22%) tested positive for HIV. In adjusted models, married Indian women experiencing both physical and sexual violence from husbands demonstrated elevated HIV infection prevalence vs those not experiencing IPV (0.73% vs 0.19%; adjusted OR, 3.92; 95% CI, 1.41-10.94; P = .01

[Efficiency of hemoperfusion on clearing thallium based on atomic absorption spectrometry].

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Tian, Tian; Wang, Yongan; Nie, Zhiyong; Wang, Jiao; Peng, Xiaobo; Yuan, Ye; Li, Wanhua; Qiu, Zewu; Xue, Yanping; Xiong, Yiru

2015-04-01

To determine thallium in whole blood by atomic absorption detection method, and to investigate the eliminating effect of hemoperfusion (HP) for thallium in blood. The blood of Beagle dogs which had not exposed to thallium before were obtained for preparation of thallium nitrate ( TlNO3 )-containing solution in three concentrations according to the conversion formula based on animal weight and volume of blood. HP was performed in the simulated in vivo environment. The content of TlNO3 in blood of the next group was determined on the amount of TlNO3 for the last HP of the former dose group. Thallium quantity in different samples was measured with atomic absorption spectrometer blood samples before and after HP. Finally, the thallium concentration in blood was analyzed statistically. Thallium concentrations showed a good linear relationship in the range of 0-200 μg/L (r = 0.998 4). The intra-day precision (RSD) was lower than 4.913%, the intra-day recovery rate was 96.2%-111.9%; the inter-day precision (RSD) was lower than 7.502%, the inter-day recovery rate was 89.6%-105.2%. The concentration of thallium in blood was significantly reduced after HP per time in high, middle, and low dose groups [(453.43 ± 27.80) mg/L to (56.09 ± 14.44) mg/L in high dose group, F = 8.820, P = 0.003; (64.51 ± 13.60) mg/L to (3.19 ± 0.23) mg/L in middle dose group, F = 36.312, P = 0.000; (5.40 ± 0.98) mg/L to (0.38 ± 0.25) mg/L in low dose group, F = 46.240, P = 0.000 ]. The adsorption rate of four times of HP in high, middle and low dose group were (87.63 ± 2.48 )%, (95.06 ± 1.54 )% and (92.76 ± 4.87)%, respectively, without significant difference (F = 4.231, P = 0.070). The method for measuring thallium was established, and it shows a very stable, simple, sensitive for determination of thallium. HP can effectively remove thallium from blood. Thallium concentration can be reduced by 90% after four times of HP. HP is also effective even when thallium concentration is not high.

Reworking of Archean mantle in the NE Siberian craton by carbonatite and silicate melt metasomatism: Evidence from a carbonate-bearing, dunite-to-websterite xenolith suite from the Obnazhennaya kimberlite

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Ionov, Dmitri A.; Doucet, Luc S.; Xu, Yigang; Golovin, Alexander V.; Oleinikov, Oleg B.

2018-03-01

The Obnazhennaya kimberlite in the NE Siberian craton hosts a most unusual cratonic xenolith suite, with common rocks rich in pyroxenes and garnet, and no sheared peridotites. We report petrographic and chemical data for whole rocks (WR) and minerals of 20 spinel and garnet peridotites from Obnazhennaya with Re-depletion Os isotope ages of 1.8-2.9 Ga (Ionov et al., 2015a) as well as 2 pyroxenites. The garnet-bearing rocks equilibrated at 1.6-2.8 GPa and 710-1050 °C. Some xenoliths contain vermicular spinel-pyroxene aggregates with REE patterns in clinopyroxene mimicking those of garnet. The peridotites show significant scatter of Mg# (0.888-0.924), Cr2O3 (0.2-1.4 wt.%) and high NiO (0.3-0.4 wt.%). None are pristine melting residues. Low-CaO-Al2O3 (≤0.9 wt.%) dunites and harzburgites are melt-channel materials. Peridotites with low to moderate Al2O3 (0.4-1.8 wt.%) usually have CaO > Al2O3, and some have pockets of calcite texturally equilibrated with olivine and garnet. Such carbonates, exceptional in mantle xenoliths and reported here for the first time for the Siberian mantle, provide direct evidence for modal makeover and Ca and LREE enrichments by ephemeral carbonate-rich melts. Peridotites rich in CaO and Al2O3 (2.7-8.0 wt.%) formed by reaction with silicate melts. We infer that the mantle lithosphere beneath Obnazhennaya, initially formed in the Mesoarchean, has been profoundly modified. Pervasive inter-granular percolation of highly mobile and reactive carbonate-rich liquids may have reduced the strength of the mantle lithosphere leading the way for reworking by silicate melts. The latest events before the kimberlite eruption were the formation of the carbonate-phlogopite pockets, fine-grained pyroxenite veins and spinel-pyroxene symplectites. The reworked lithospheric sections are preserved at Obnazhennaya, but similar processes could erode lithospheric roots in the SE Siberian craton (Tok) and the North China craton, where ancient melting residues and

Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

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Mir, Fatima; Nisar, Imran; Tikmani, Shiyam S; Baloch, Benazir; Shakoor, Sadia; Jehan, Fyezah; Ahmed, Imran; Cousens, Simon; Zaidi, Anita K M

2017-02-01

Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and

Vegetation, climate and fire-dynamics in East Africa inferred from the Maundi crater pollen record from Mt Kilimanjaro during the last glacial-interglacial cycle

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Schüler, Lisa; Hemp, Andreas; Zech, Wolfgang; Behling, Hermann

2012-04-01

The pollen, charcoal and sedimentological record from the Maundi crater, located at 2780 m elevation on the south-eastern slope of Mt Kilimanjaro, is one of the longest terrestrial records in equatorial East Africa, giving an interesting insight into the vegetation and climate dynamics back to the early last Glacial period. Our sediment record has a reliable chronology until 42 ka BP. An extrapolation of the age-depth model, as well as matching with other palaeo-records from tropical East Africa, suggest a total age of about 90 ka BP at the bottom of the record. During the last Glacial the distribution as well as the composition of the vegetation belts classified as colline savanna, submontane woodland, montane forest, ericaceous belt, and alpine vegetation changed. The early last Glacial is characterized by high amounts of Poaceae and Asteraceae pollen suggesting a climatically dry but stable phase. Based on the absence of pollen grains in samples deposited around 70 ka BP, we assume the occurrence of distinct drought periods. During the pre-LGM (Last Glacial Maximum) a higher taxa diversity of the ericaceous and montane zone is recorded and suggests a spread of forest and shrub vegetation, thus indicating a more humid period. The taxa diversity increases steadily during the recorded time span. The decent of vegetation zones indicate dry and cold conditions during the LGM and seem to have been detrimental for many taxa, especially those of the forest vegetation; however, the early last Glacial seems to have been markedly drier than the LGM. The reappearance of most of the taxa (most importantly Alchemilla, Araliaceae, Dodonea, Hagenia, Ilex, Myrsine, Moraceae, Piperaceae) during the deglacial and Holocene period suggest a shift into humid conditions. An increase in ferns and the decrease in grasses during the Holocene also indicate increasing humidity. Fire played an important role in controlling the development and elevation of the ericaceous zone and the tree

CYP2C19*2 status in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis

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Laska AJ

2017-05-01

Full Text Available Amanda J Laska,1 Marie J Han,1 Josh A Lospinoso,2 Patrick J Brown,1 Thomas M Beachkofsky1 1Department of Dermatology, San Antonio Uniformed Services Health Education Consortium, San Antonio, TX, 2780th Military Intelligence Brigade, Ft Meade, MD, USA Purpose: Genetic polymorphisms have been linked to an increased predisposition to developing certain diseases. For example, patients of Han-Chinese descent carrying the HLA-B*1502 allele are at an increased risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN if given carbamazepine. Given the complexity of in vivo drug metabolism, it is plausible that the activity of enzyme systems unrelated to specific drug metabolism may be important. Although multiple biomarkers have been identified in unique ethnic groups, there has yet to be a study investigating the presence of the slow metabolizing allele of CYP2C19, denoted CYP2C19*2, in diverse groups and the risk of developing SJS/TEN. Patients and methods: This study looked into the carrier status of CYP2C19*2, a poor metabolizing variant of CYP2C19, in patients diagnosed with SJS/TEN. We looked at its status in our series as a whole and when patients were divided by ethnicity. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue of patients with biopsy-proven SJS/TEN and real-time polymerase chain reaction was used to assess for the presence of CYP2C19*2. Results: CYP2C19*2 status was determined in 47 patients. Twenty-nine of these 47 patients had a single medication implicated as causing their disease, and eight of these patients were heterozygous or homozygous for CYP2C19*2. There was insufficient evidence to conclude that the presence of CYP2C19*2 is an independent predictor of risk for developing SJS/TEN in our series as a whole. This analysis also confirmed that the frequency of the CYP2C19*2 polymorphism within the different ethnicities in our series did not vary statistically from reported ethnic

Bithionol inhibits ovarian cancer cell growth In Vitro - studies on mechanism(s) of action

International Nuclear Information System (INIS)

Ayyagari, Vijayalakshmi N; Brard, Laurent

2014-01-01

Drug resistance is a cause of ovarian cancer recurrence and low overall survival rates. There is a need for more effective treatment approaches because the development of new drug is expensive and time consuming. Alternatively, the concept of ‘drug repurposing’ is promising. We focused on Bithionol (BT), a clinically approved anti-parasitic drug as an anti-ovarian cancer drug. BT has previously been shown to inhibit solid tumor growth in several preclinical cancer models. A better understanding of the anti-tumor effects and mechanism(s) of action of BT in ovarian cancer cells is essential for further exploring its therapeutic potential against ovarian cancer. The cytotoxic effects of BT against a panel of ovarian cancer cell lines were determined by Presto Blue cell viability assay. Markers of apoptosis such as caspases 3/7, cPARP induction, nuclear condensation and mitochondrial transmembrane depolarization were assessed using microscopic, FACS and immunoblotting methods. Mechanism(s) of action of BT such as cell cycle arrest, reactive oxygen species (ROS) generation, autotaxin (ATX) inhibition and effects on MAPK and NF-kB signalling were determined by FACS analysis, immunoblotting and colorimetric methods. BT caused dose dependent cytotoxicity against all ovarian cancer cell lines tested with IC 50 values ranging from 19 μM – 60 μM. Cisplatin-resistant variants of A2780 and IGROV-1 have shown almost similar IC 50 values compared to their sensitive counterparts. Apoptotic cell death was shown by expression of caspases 3/7, cPARP, loss of mitochondrial potential, nuclear condensation, and up-regulation of p38 and reduced expression of pAkt, pNF-κB, pIκBα, XIAP, bcl-2 and bcl-xl. BT treatment resulted in cell cycle arrest at G1/M phase and increased ROS generation. Treatment with ascorbic acid resulted in partial restoration of cell viability. In addition, dose and time dependent inhibition of ATX was observed. BT exhibits cytotoxic effects on various

Polysulfides and products of H2S/S-nitrosoglutathione in comparison to H2S, glutathione and antioxidant Trolox are potent scavengers of superoxide anion radical and produce hydroxyl radical by decomposition of H2O2.

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Misak, Anton; Grman, Marian; Bacova, Zuzana; Rezuchova, Ingeborg; Hudecova, Sona; Ondriasova, Elena; Krizanova, Olga; Brezova, Vlasta; Chovanec, Miroslav; Ondrias, Karol

2018-06-01

Exogenous and endogenously produced sulfide derivatives, such as H 2 S/HS - /S 2- , polysulfides and products of the H 2 S/S-nitrosoglutathione interaction (S/GSNO), affect numerous biological processes in which superoxide anion (O 2 - ) and hydroxyl (OH) radicals play an important role. Their cytoprotective-antioxidant and contrasting pro-oxidant-toxic effects have been reported. Therefore, the aim of our work was to contribute to resolving this apparent inconsistency by studying sulfide derivatives/free radical interactions and their consequent biological effects compared to the antioxidants glutathione (GSH) and Trolox. Using the electron paramagnetic resonance (EPR) spin trapping technique and O 2 - , we found that a polysulfide (Na 2 S 4 ) and S/GSNO were potent scavengers of O 2 - and cPTIO radicals compared to H 2 S (Na 2 S), GSH and Trolox, and S/GSNO scavenged the DEPMPO-OH radical. As detected by the EPR spectra of DEPMPO-OH, the formation of OH in physiological solution by S/GSNO was suggested. All the studied sulfide derivatives, but not Trolox or GSH, had a bell-shaped potency to decompose H 2 O 2 and produced OH in the following order: S/GSNO > Na 2 S 4  ≥ Na 2 S > GSH = Trolox = 0, but they scavenged OH at higher concentrations. In studies of the biological consequences of these sulfide derivatives/H 2 O 2 properties, we found the following: (i) S/GSNO alone and all sulfide derivatives in the presence of H 2 O 2 cleaved plasmid DNA; (ii) S/GSNO interfered with viral replication and consequently decreased the infectivity of viruses; (iii) the sulfide derivatives induced apoptosis in A2780 cells but inhibited apoptosis induced by H 2 O 2 ; and (iv) Na 2 S 4 modulated intracellular calcium in A87MG cells, which depended on the order of Na 2 S 4 /H 2 O 2 application. We suggest that the apparent inconsistency of the cytoprotective-antioxidant and contrasting pro-oxidant-toxic biological effects of sulfide derivatives results from their time

Temperature and precipitation records from stalagmites grown under disequilibrium conditions: A model approach.

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Mühlinghaus, C.; Scholz, D.; Mangini, A.

2009-04-01

records of the stalagmites, which were obtained by three independent model runs, follow a general trend over the whole growth period and reveal good correlations within certain time-frames. This is a promising first result of the model. In addition the calculated temperatures are robust to small variations of the input variables, giving confidence in the algorithm of the model and for further temperature reconstructions from kinetically grown stalagmites. Literature Dreybrodt, W., 1999. Chemical kinetics, speleothem growth and climate. Boreas 28, 347 -356. Kaufmann, G., Dreybrodt, W. , 2004. Stalagmite growth and palaeo-climate: an inverse approach. Earth and Planetary Science Letters 224, 529 - 545. Kilian, R., Biester, H., Behrmann, J., Baeza, O., Fesq-Martin, M., Hohner, M., Schimpf, D., Friedmann, A., Mangini, A., 2006: Millennium-scale volcanic impact on a superhumid and pristine ecosystem, Geology, 34: 609 - 612. Mühlinghaus, C., Scholz, D., Mangini, A., 2007. Modelling stalagmite growth and ^13C as a function of drip interval and temperature. Geochimica et Cosmochimica Acta 71, 2780 - 2790. Mühlinghaus, C.; Scholz, D., Mangini, A., 2008a. Temperature and precipitation records from stalagmites grown under disequilibrium conditions: A first approach. Advances in speleothem research, PAGES News, 16 Mühlinghaus, C., Scholz, D., Mangini, A., 2008b. Fractionation of stable isotopes in stalagmites under disequilibrium conditions. Geochimica et Cosmochimica Acta, Submitted. Schimpf, D., 2005. Datierung und Interpretation der Kohlenstoff- und Sauerstoffsotopie zweier holozäner Stalagmiten aus dem Süden Chiles (Patagonien). Master's thesis, Ruprecht-Karls- University, Heidelberg. Schimpf, D., Kilian, R., Mangini, A., Spötl, C., Kronz, A., in prep. Evaluation of chemical, isotopic and detrital proxies of a high-resolution stalagmite record from the southernmost Chilean Andes (53˚ S) Scholz, D., Mühlinghaus, C., Mangini, A., 2008. Modelling the evolution of ^13C and

Occurrence and fate of the norsesquiterpene glucoside ptaquiloside (PTA) in soils

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Zaccone, Claudio; Cavoski, Ivana; Costi, Roberta; Sarais, Giorgia; Caboni, Pierluigi; Miano, Teodoro M.; Lattanzio, Vincenzo

2014-05-01

The bracken fern Pteridium aquilinum (L.) Kuhn, one of the most common plant species on Earth, produces a wide range of secondary metabolites including the norsesquiterpene glucoside ptaquiloside (PTA). This bracken constituent causes acute poisoning, blindness and cancer in animals, and can be transferred to man when bracken is utilized as food. Also milk from cows eating bracken is thought to be the vector for the transfer of PTA to humans, as well as PTA-contaminated drinking waters. Although some studies on the effect of growth conditions and soil properties on the production and mobility of PTA have been carried out (mainly in the North of Europe), results are sometimes conflicting and further investigations are needed. The aim of the present work is to study the occurrence and the fate of PTA in soils showing different physico-chemical features, collected in different pedoclimatic areas (from the South of Italy), but having the extensive ("wild") livestock farming as common denominator. The PTA content was determined in both soil and fern samples by GC-MS; both the extraction protocol and recovery were previously tested through incubation studies. Soils samples were also characterizes from the physical and chemical point of view (pH, EC, texture, total carbonates, cation exchange capacity, organic C, total N, available nutrients and heavy metal concentration) in order to correlate the possible influence of soil parameters on PTA production, occurrence and mobility. PTA concentration in soil samples was always 2-780 µg/g), ii) the soil organic matter content (ranging from 3.4 to 22.8%), iii) the soil pH (ranging from 5.9 to 6.6), iv) the soil texture, v) the depth (0-10 cm; 10-20 cm), and vi) precipitations (ranging from 780 to 960 mm/a). This seems to suggest the degradation of the PTA by indigenous microbial community

[Liposome-mediated glial growth factor 2 gene therapy in brain injury: an experimental study with rats].

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Xue, Ya-jun; Dong, Yan; Han, Xi; Wei, Mei-yang; Ge, Jun-hui; Cai, Ru-jue; Hu, Guo-han; Luo, Chun; Zhu, Cheng; Lu, Yi-cheng

2006-09-05

To explore the protective effect of glial growth factor-2 (GGF2) on brain injury. Thirty-four SD rats underwent lateral fluid percussion to establish brain injury models and then were randomly divided into 4 groups: treatment group (n = 10, the plasmid pEGFP-N1-GGF2 mixed with liposome was injected into the brain tissue directly), vector control group (n = 10, the vector pEGFP-N1 mixed with liposome was injected into the brain tissue directly), liposome control group (n = 10, liposome was injected), and sham operation group (n = 4). Three assessment tasks were performed for neurobehavioral evaluation: Clivas Test, Beam Balance Test and Beam Walking Test. 10 days after brain injury, the rats were sacrificed and their brains were embedded in paraffin for HE staining, Nissle staining and immunohistochemical examination of MBP, NSE, and GFAP. The Clivas test score of the treatment group was 66.25 +/- 3.54, significantly higher than those of the vector control group and. liposome control group (58.31 +/- 3.72 and 57.21 +/- 3.93 respectively, both P beam test score of the treatment group was 2.59 +/- 0.21, significantly lower than those the vector control group and liposome control group (3.41 +/- 0.25 and 3.24 +/- 0.22 respectively, both P walking test score of the treatment group was 20.15 +/- 2.59, significantly lower than those of control group and liposome control group (27.00 +/- 3.47 and 27.80 +/- 3.00 respectively, both P beam walking test was the greatest. The neuron number in the external granular layer and external pyramidal layer in cortex of the treatment group was 98 +/- 10, significantly more than those of the vector control group and liposome group (75 +/- 7 and 67 +/- 8, both P < 0.05). The neuron number in the internal pyramidal layer in cortex of the treatment group was 37 +/- 4, significantly more than those of the vector control group and liposome group (19 +/- 3 and 23 +/- 4 respectively, both P < 0.05). The neuron number in the CA1 region in

Archaean TTG of Vodlozero Terrain, Fennoscandian Shield

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Chekulaev, Valery; Arestova, Natalia

2014-05-01

The Vodlozero terrain is the largest (about 270*240 km) early Archaean fragment of Fennoscandian Shield and composes its eastern part. The granitoids of TTG suite are predominant component of the terrain. The greenstone belts are placed along the margins of the terrain. Several stages of TTG formation can be distinguished in Achaean crust history. (1) The oldest TTG are trondhjemites and tonalities with age of 3240 Ma. They contain rare and small amphibolite inclusions of the same age. These TTG are characterized by high Sr (av. 412 ppm), Sr/Y (70), (La/Yb)n (54) and low Y (av. 7 ppm), Yb (0.32 ppm) and Nb (4 ppm). It was shown (Lobach-Zhuchenko et al., 2000), that the source of these TTG could be basic rocks, having composition similar with TH1 by K.Condie. (2) The tonalities and granodiorites with age of 3150 Ma are disposed near greenstone belts and contain compared to TTG of the first group less Sr (av. 250 ppm), Sr/Y (22), (La/Yb)n (18) and more K, Rb (av. 70 ppm), Ba (470 ppm), Y (11 ppm),Yb (1.16 ppm). TTG of both groups have identical T(DM)Nd (3250-3400 Ma) and differences in composition is evidently connected with lower level of source melting of the second group and also with K-metasomatism. The volcanics of the greenstone belts have age 3020 - 2940 Ma. Dykes of gabbro-amphibolites and andesites with the same age and composition cut TTG of the first and the second groups. The age of the third TTG group is about 2900 Ma ago. These rocks form leucosoma of migmatites within TTG of the second group. The composition of the third TTG and Nd isotope data suppose their origin by the melting of ancient TTG crust simultaneously with greenstone belt emplacement. The fourth TTG group with age 2780-2850 Ma forms a small intrusions, cutting older TTG and greenstone rocks. Their composition is similar to 3150 Ma TTG. Nd isotope data indicate that these TTG have younger (about 2850 Ma) source. Thus there are four TTG groups formed into interval more 400 Ma. The age and

Technology for collecting and analyzing relational data

Directory of Open Access Journals (Sweden)

E. N. Fedorova

2016-01-01

summarize the information there is a mechanism of data grouping, which provides general data of the number of entries, maximum, minimum, average values for different groups of records.Results. This technology has been tested in the monitoring requirements of the services of additional professional education and the definition of the educational needs of teachers and executives of educational organizations of the Irkutsk region. The survey has involved 2,780 respondents in 36 municipalities. Creating the data model took several hours. The survey was conducted during the month.Conclusion. The proposed technology allows a short time to collect the information in relational form, and then analyze it without the need for programming with flexible assignment of the operating logic for form.

Evaluation of the secondary cardiotoxicity to use adriamycin in patients with breast cancer with nuclear medicine studies

International Nuclear Information System (INIS)

Garcia P, S.

2003-01-01

The number of surviving of cancer is increased highly with the current regimes of chemotherapy. For the year 2010 in U.S. it is considered that one of each 250 adults can be a survivor of wicked illness and many of these survivors will have been exposed to regimes with anthracycline. The anthracyclines concern to the group of antibiotics and they are effective point for hematological neoplasms as solid tumors. Although the relationship dose answer, among the regimes with anthracycline as well as the remission and the period free of illness is very established one, the latent risk of cardiotoxicity limits the use of these agents. Results: 30 patients were recruited with diagnostic of invader breast cancer tried with chemotherapy to base anthracycline in the understood period of may to december of the 2000. The medium of age it was of 48 years with a range of 27-80 years. The clinical stage that prevailed it was the EC IIB that represents a 36% in second place the EC IIIA with a 20%, EC IIA with 16% the EC IIIB and the unclassifiable ones represented 10% with 3 patients and finally the clinical stage IV with 8%, the most frequent localization was the left side.The received chemotherapy outline it was with the base of doxorubicin in its modality neo or patient adjutant, 5 patients also received taxanes like treatment adjutant. Prevailed the continuous infusion in 24 hours in 50%. The medium of accumulated dose of adriamycin was 274 mg/m 2 . With a left ventricular ejection fraction LVEF pretreatment of 62% (medium) determined by VRI and a medium of 69% by SPECT. The LVEF pos treatment had one medium of 57% for VRI and by SPECT a medium of 60%. They received concomitant radiotherapy with chemotherapy in modality pre operation 53.3% (16 patients), and 40% radiotherapy post operation, 2 patients didn't receive radiotherapy. In relation to the heart toxicity any patient present electrocardiographic alterations, neither arrhythmias neither clinical data of heart congestive

Evaluation of the secondary cardiotoxicity to use adriamycin in patients with breast cancer with nuclear medicine studies; Evaluacion de la cardiotoxicidad secundaria al empleo de adriamicina en pacientes con cancer de mama con estudios de medicina nuclear

Energy Technology Data Exchange (ETDEWEB)

Garcia P, S

2003-07-01

The number of surviving of cancer is increased highly with the current regimes of chemotherapy. For the year 2010 in U.S. it is considered that one of each 250 adults can be a survivor of wicked illness and many of these survivors will have been exposed to regimes with anthracycline. The anthracyclines concern to the group of antibiotics and they are effective point for hematological neoplasms as solid tumors. Although the relationship dose answer, among the regimes with anthracycline as well as the remission and the period free of illness is very established one, the latent risk of cardiotoxicity limits the use of these agents. Results: 30 patients were recruited with diagnostic of invader breast cancer tried with chemotherapy to base anthracycline in the understood period of may to december of the 2000. The medium of age it was of 48 years with a range of 27-80 years. The clinical stage that prevailed it was the EC IIB that represents a 36% in second place the EC IIIA with a 20%, EC IIA with 16% the EC IIIB and the unclassifiable ones represented 10% with 3 patients and finally the clinical stage IV with 8%, the most frequent localization was the left side.The received chemotherapy outline it was with the base of doxorubicin in its modality neo or patient adjutant, 5 patients also received taxanes like treatment adjutant. Prevailed the continuous infusion in 24 hours in 50%. The medium of accumulated dose of adriamycin was 274 mg/m{sup 2}. With a left ventricular ejection fraction LVEF pretreatment of 62% (medium) determined by VRI and a medium of 69% by SPECT. The LVEF pos treatment had one medium of 57% for VRI and by SPECT a medium of 60%. They received concomitant radiotherapy with chemotherapy in modality pre operation 53.3% (16 patients), and 40% radiotherapy post operation, 2 patients didn't receive radiotherapy. In relation to the heart toxicity any patient present electrocardiographic alterations, neither arrhythmias neither clinical data of heart

[Effect of the night shift work on micturition patterns of nurses].

Science.gov (United States)

Wang, Q; Hu, H; Liang, C; Wang, J; Xu, K X

2016-08-18

To compare the effects of rotational night shifts on the micturition patterns of female nurses. A total of 58 nurses without lower urinary tract symptoms were recruited, who worked in the Peking University People's Hospital during January and June in 2014. The nurses aged 20-43 years were divided into two groups, the night-shift group (n=28) and the non-shift group (n=30). The alcohol or coffee intaking were forbidden. In the night-shift group, nurses had worked on rotational shifts for at least 6 months. Their average age was (26.75±4.11) years. In the non-shift group, nurses took regular day-time work, whose average age was (27.80±5.60) years. A voiding diary was kept for 7 consecutive days at the end of 6 months, starting 2 days before their night duties until 4 days after completion of their night duties. For comparison, the non-shift group with regular shifts completed a 7-day voiding diary. In the 7-day recording voiding diary, the nurses were required to have the normal intake of liquid about 1 500-2 000 mL/d. The frequency volume charts of nocturia, the 8-hour interval urine production and frequency were compared between the two groups. Nocturia frequency was increased in the night-shift group [0.5 (0-2.4)] compared with the non-shift group [0 (0-2), P=0.02]. The volume of nocturia was increased in the night-shift group [125 mL (0-660 mL)] compared with the non-shift group [0 mL (0-340 mL), Pshift (Pnight-shift group increased on the day after night shift. When the night-shift nurses returned to daytime duty, the volume of urine decreased but nocturnal urine production remained high, and the frequency of nocturia also increased significantly (Pnight-shift group's voiding volume [(542.35±204.66) mL] and voiding frequency (2.24±0.69) were more than those of the non-shift group at the afternoon time (from 2 pm to 10 pm). During the 8 h interval night time (from 10 pm to 6 am), the volume of nocturia in the night-shift group [(309.74±162.74) mL] was more

Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific

Energy Technology Data Exchange (ETDEWEB)

Taki, Junichi; Nakajima, Kenichi; Hwang, Eui-Hyo; Matsunari, Ichiro; Tonami, Norihisa [Department of Nuclear Medicine, Kanazawa University School of Medicine, Kanazawa (Japan); Komai, Kiyonobu; Yoshita, Mitsuhiro; Sakajiri, Kenichi [Department of the Neurology, Kanazawa University School of Medicine, Kanazawa (Japan)

2000-05-01

The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63{+-}9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61{+-}0.29) was significantly lower than that in the control group (2.24{+-}0.14, P<0.01), P-nism (2.15{+-}0.31, P<0.01), MSA (2.08{+-}0.31, P<0.05) and PSP (2.30{+-}0.24, P<0.01). The delayed H/M ratio in PD (1.47{+-}0.34) was also significantly lower than that in the control group (2.37{+-}0.14, P<0.01), P-nism (2.13{+-}0.38, P<0.01), PSP (2.36{+-}0.36, P<0.01) and MSA (2.17{+-}0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%{+-}8.0% vs 11%{+-}4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus—a prospective, population-based cohort study

Science.gov (United States)

Ollila, M.-M.E.; West, S.; Keinänen-Kiukaanniemi, S.; Jokelainen, J.; Auvinen, J.; Puukka, K.; Ruokonen, A.; Järvelin, M.-R.; Tapanainen, J.S.; Franks, S.; Piltonen, T.T.; Morin-Papunen, L.C.

2017-01-01

STUDY QUESTION What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? SUMMARY ANSWER The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. WHAT IS KNOWN ALREADY PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. STUDY DESIGN, SIZE, DURATION In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. PARTICIPANTS/MATERIALS, SETTING, METHODS Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. MAIN RESULTS AND THE ROLE OF CHANCE PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m2) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28–4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus-a prospective, population-based cohort study.

Science.gov (United States)

Ollila, M-M E; West, S; Keinänen-Kiukaanniemi, S; Jokelainen, J; Auvinen, J; Puukka, K; Ruokonen, A; Järvelin, M-R; Tapanainen, J S; Franks, S; Piltonen, T T; Morin-Papunen, L C

2017-02-01

What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m 2 ) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28-4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years was significantly greater in women with PCOS developing T2DM than in women with PCOS and normal glucose tolerance, with the most significant increase occurring

Thermodynamics of natural tourmalines—Dravite and schorl

International Nuclear Information System (INIS)

Ogorodova, L.P.; Melchakova, L.V.; Kiseleva, I.A.; Peretyazhko, I.S.

2012-01-01

Highlights: ► Heat capacity of natural tourmalines (dravite and schorl) was measured within 270–700 K. ► The enthalpy increments at interval of 712–973 K were measured. ► The C p,m °(T) equations for dravite and schorl were calculated. ► The values of Δ f H m °(298.15K) of dravite and schorl were determined by solution calorimetry. ► The estimation of thermodynamic properties of six tourmaline end-members was made. - Abstract: The experimental data on the heat capacities and enthalpies of formation from the elements of two natural tourmalines: dravite (Na 0.53 Ca 0.31 K 0.03 )(Mg 2.72 Al 6.22 Li 0.02 Ti 0.08 Fe 0.12 2+ )Si 5.92 B 2.92 (OH) 2.85 F 0.27 O 27.59 and schorl (Na 0.82 Ca 0.13 K 0.03 )(Fe 2.23 2+ Fe 0.22 3+ Al 5.90 Mg 0.28 Mn 0.09 Li 0.02 Ti 0.11 ) Si 6.04 B 3.11 (OH) 3.00 F 0.02 O 27.80 have been obtained. The heat capacities were measured by DSC method from T = 270 K to 700 K. High-temperature enthalpy increments were determined on the Tian–Calvet microcalorimeter at interval of 712–973 K using the “drop” method. The values of C p,m °(298.15K)=780.6 J K −1  mol −1 for dravite and 794.2 J K −1 mol −1 for schorl were obtained and the resultant C p,m °(T) equation in the interval T = 298.15–973 K were calculated: C p,m °=1166.3+80.5×10 −3 T−364.2×10 5 T −2 , J K −1  mol −1 , (±2.4%) J K −1 mol −1 and C p,m °=1016.5+346.8×10 −3 T−289.5×10 5 T −2 , J K −1  mol −1 , (±3.7%) at 298.15–973 K J K −1 mol −1 , respectively. The standard molar enthalpies of formation from the elements were determined by high-temperature solution calorimetry in molten lead borate at T = 973 K on the Tian–Calvet microcalorimeter. The values of Δ f H m °(298.15K) were found to be −15,410 ± 24 kJ mol −1 for dravite and −14,500 ± 44 kJ mol −1 for schorl. The estimation of thermodynamic properties of six tourmaline end-members was made.

Multiproxy Holocene paleoclimate records from the southern Peruvian Andes - what new can we learn from the stable carbon isotope composition of high altitude organic matter deposits?

Science.gov (United States)

Skrzypek, Grzegorz; Engel, Zbyněk

2015-04-01

Interpretation of the Central Andean paleoclimate over the last millennia still represents a research challenge demanding deeper studies [1,2]. Several high-resolution paleoclimate proxies for the last 10,000 years have been developed for the northern hemisphere. However, similar proxies are very limited for South America, particularly for high altitudes where, for example, tree-ring chronologies are not available and instrumental records are very limited. Consequently, our knowledge of high altitude climate changes in arid regions of the Peruvian Andes mainly relies on ice-core and lake deposit studies. In our study, we used a new alternative proxy for interpretation of palaeoclimate conditions based on a peat core taken from the Carhuasanta Valley at the foot of Nevado Mismi in the southern Peruvian Andes (15° 30'S, 71° 43'W, 4809m a.s.l.). The stable carbon isotope composition (δ13C) of Distichia peat reflects mainly the relative variation of the mean air temperature during subsequent growing seasons [3], and allows reconstructions of palaeotemperature changes. In contrast, peat organic carbon concentration (C % wt) records mainly wetness in the valley, directly corresponding to the changes in runoff in the upper part of the catchment. The most prominent climate changes recorded in the peat over last 4ka occurred between 3040 and 2750 cal. yrs BP. The initial warming turned to a very rapid cooling to temperatures at least 2° C lower than the mean for the Late Holocene. Initially drier conditions within this event turned to a short wet phase after 2780 cal. yrs BP, when the temperature increased again. This event coincides with significant changes in peat and ice core records in the Central Andes that match the timing of the global climate event around 2.8 cal. ka BP. Climatic conditions in the study area became relatively dry and stable after the event for about 800 years. Highly variable temperatures and humidity prevailed during the last 2000 years, when

The 87Sr/86Sr aquatic isoscape of the Danube catchment from the source to the mouth as tool for studying fish migrations

Science.gov (United States)

Zitek, Andreas; Tchaikovsky, Anastassiya; Irrgeher, Johanna; Waidbacher, Herwig; Prohaska, Thomas

2014-05-01

Isoscapes - spatially distributed isotope patterns across landscapes - are increasingly used as important basis for ecological studies. The natural variation of the isotopic abundances in a studied area bears the potential to be used as natural tracer for studying e.g. migrations of animals or prey-predator relations. The 87Sr/86Sr ratio is one important tracer, since it is known to provide a direct relation of biological samples to geologically distinct regions, as Sr isotopes are incorporated into living tissues as a proxy for calcium and taken up from the environment without any significant fractionation. Although until now the focus has been mainly set on terrestrial systems, maps for aquatic systems are increasingly being established. Here we present the first 87Sr/86Sr aquatic isoscape of the Danube catchment, the second largest river catchment in Europe, from near its source starting at river km 2581 in Germany down to its mouth to river km 107 in Romania. The total length of the river Danube is 2780 km draining a catchment area 801 463 km2 (10 % of the European continent). The major purpose of this study was to assess the potential of the 87Sr/86Sr isotope ratio to be used as tool for studying fish migrations at different scales in the entire Danube catchment. Within the Joint Danube Research 3 (JDS 3), the biggest scientific multi-disciplinary river expedition of the World in 2013 aiming at the assessment of the ecological status and degree of human alterations along the river Danube, water samples were taken at 68 pre-defined sites along the course of the river Danube including the major tributaries as a basis to create the so called 'Isoscape of the Danube catchment'. The determination of 87Sr/86Sr isotope ratio in river water was performed by multicollector-sector field-inductively coupled plasma-mass spectrometry (MC-SF-ICP-MS). The JDS 3 data were combined with existing data from prior studies conducted within the Austrian part of the Danube catchment

Understanding the residence of Co in ore minerals - towards the development of novel Co extraction strategies for laterite deposits

Science.gov (United States)

Dybowska, Agnieszka; Norman, Rachel; Schofield, Paul; Herrington, Richard

2017-04-01

Cobalt has unique properties highly valued for many applications essential to the green economy. It has been classified as a critical raw material due to the particularly high risk of supply shortage and its importance for the value chain. Despite low crustal abundance (25ppm), Co is concentrated by various geological processes to concentrations suitable for mining, however the majority of Co is recovered as a by-product of Cu and Ni processing in three principal geological settings: hydrothermal, magmatic and lateritic. Cobalt-rich laterites, which provide 20% of the world's Co, are mainly processed using energy-inefficient pyrometallurgical techniques or high-pressure acid leaching technologies often optimised for extraction of other elements, which can leave between 50 and 80% of the Co unrecovered. In order to develop more efficient Co extraction strategies, understanding the residence of Co in ore minerals is essential. To this end, we are undertaking a detailed mineralogical, chemical and atomistic-scale characterization of Co in samples from a range of laterite deposits. Bulk samples representative of the average ore material were sourced from a variety of undeveloped laterite deposits: Shevchenko (Kazakhstan), Acoje (Philippines), Nkamouna (Cameroon) and Piauí (Brazil). Bulk chemical and mineralogical characterisation was undertaken with ICP-OES/MS and XRD, followed by spatially resolved chemical and mineralogical imaging at the micron scale using µXRD, EPMA, SEM and synchrotron-based µXRF. The chemical state and local environment of Co were determined using X ray spectroscopy (μXANES and μEXAFS). The total concentrations of Co ranged from 630 to 2780 mg/kg. The ore mineral assemblage in the various samples includes goethite, maghemite, hematite, quartz, talc, serpentines, chlorites, smectites, kaolinite and chromites. Manganese oxide minerals are present but, due to their poor crystallinity and low concentration, are not routinely detectable with bulk

WAYS TO IMPROVE PREVENTION OF CHICKENPOX AT CHILDREN OF UKRAINE IN MODERN CONDITION

Directory of Open Access Journals (Sweden)

Kirsanova T.O.

2015-05-01

Full Text Available Introduction. Chickenpox (CP in recent years has tended to steady increase in the incidence of various regions of Ukraine, especially among children. The situation regarding the incidence of PA nowadays, especially among children, determines the relevance of infection and requires the solution of problems in finding the most effective ways to prevent the population of Ukraine against CP. Purpose: to theoretically justify the introduction of the National vaccination calendar of Ukraine vaccine against CP based on the study of modern epidemiological, clinical and paraclinical features of CP in children of Kharkiv region of Ukraine. Materials and methods. The analysis of statistical data on the incidence of PA in Kharkiv region and 2780 data from case histories of children aged one month PA-18, admitted to the Kharkiv Regional Hospital of Pediatric Infectious Diseases in the last five years. The diagnosis is established on the basis of characteristic clinical manifestations. Results and discussion. During the period 2010-2014 epidemiological curve morbidity in children with CP has tended to rise with maximum performance in 2011, prevailed among patients, children who lived in the city. The largest recorded incidence in children under 15 years old, had a tendency to increase the proportion of high school age children. Among dominated diseased children attending organized children's groups (kindergartens, schools, including more than a third part of patients lived in closed children's institutions (orphanages, boarding schools, etc.. Clear seasonal disease was traced to the rise of the autumn-winter period. Monitoring the number of children with CP, admitted to hospital, also showed growth in their numbers. The reason for hospitalization were: pronounced intoxication syndrome, abundant rash on skin and mucous membranes, complicated disease, epidemiological indications. The most affected age groups were children 1-10 years. The disease ran mostly in

Providing physicians with feedback on medication adherence for people with chronic diseases taking long-term medication.

Science.gov (United States)

Zaugg, Vincent; Korb-Savoldelli, Virginie; Durieux, Pierre; Sabatier, Brigitte

2018-01-10

adherence may improve processes of care (e.g. more medication changes, dialogue with patient, management of uncontrolled hypertension) compared to usual care (four studies, 2780 patients). None of the studies reported an adverse event due to the intervention. The certainty of evidence was low for all outcomes, mainly due to high risk of bias, high heterogeneity across studies, and indirectness of evidence. Across nine studies, we observed little or no evidence that provision of feedback to physicians regarding their patients adherence to prescribed medication improved medication adherence, patient outcomes, or health resource use. Feedback about medication adherence may improve processes of care, but due to the small number of studies assessing this outcome and high risk of bias, we cannot draw firm conclusions on the effect of feedback on this outcome. Future research should use a clear, standardised definition of medication adherence and cluster-randomisation to avoid the risk of contamination.

Smartphone and tablet self management apps for asthma.

Science.gov (United States)

Marcano Belisario, José S; Huckvale, Kit; Greenfield, Geva; Car, Josip; Gunn, Laura H

2013-11-27

significant effect on asthma symptom scores (mean difference (MD) 0.01, 95% confidence interval (CI) -0.23 to 0.25), asthma-related quality of life (MD of mean scores 0.02, 95% CI -0.35 to 0.39), unscheduled visits to the emergency department (OR 7.20, 95% CI 0.37 to 140.76) or frequency of hospital admissions (odds ratio (OR) 3.07, 95% CI 0.32 to 29.83). The other included study found that the use of a smartphone app resulted in higher asthma-related quality of life scores at six-month follow-up (MD 5.50, 95% CI 1.48 to 9.52 for the physical component score of the SF-12 questionnaire; MD 6.00, 95% CI 2.51 to 9.49 for the mental component score of the SF-12 questionnaire), improved lung function (PEFR) at four (MD 27.80, 95% CI 4.51 to 51.09), five (MD 31.40, 95% CI 8.51 to 54.29) and six months (MD 39.20, 95% CI 16.58 to 61.82), and reduced visits to the emergency department due to asthma-related complications (OR 0.20, 95% CI 0.04 to 0.99). Both studies failed to find any statistical differences in terms of adherence to the intervention and occurrence of other asthma-related complications. The current evidence base is not sufficient to advise clinical practitioners, policy-makers and the general public with regards to the use of smartphone and tablet computer apps for the delivery of asthma self management programmes. In order to understand the efficacy of apps as standalone interventions, future research should attempt to minimise the differential clinical management of patients between control and intervention groups. Those studies evaluating apps as part of complex, multicomponent interventions, should attempt to tease out the relative contribution of each intervention component. Consideration of the theoretical constructs used to inform the development of the intervention would help to achieve this goal. Finally, researchers should also take into account: the role of ancillary components in moderating the observed effects, the seasonal nature of asthma and long

[A nurse, a historian, a writer, a teaching specialist, a care designer, and ... a woman].

Science.gov (United States)

Vigil-Ripoche, Marie-André

2011-12-01

Marie-Françoise Collière (1930-2005) was a great lady of the nursing profession recognized worldwide for her expertise. As a historian, a pioneer and an activist of the cause of the female nurses and health care, she devoted her life to giving the profession the first meaning of care, ie: accompanying the patient through his life, from the birth to the death, through disease, accident and ageing. Thus, for Marie-Françoise Collière, "Caring means health-care through the satisfaction of a series of needs which are indispensable for life but which have diverse manifestations". Here is the story of her life and her trajectory.

A Cidade e a Criança

Directory of Open Access Journals (Sweden)

Maurícia Santos de Holanda Bezerra

2013-01-01

A autora Mayumi Watanabe de Souza Lima (1934-1994 foi arquiteta, sua carreira foi dedicada ao planejamento, projeto e construção de equipamentos públicos para a educação de crianças e de jovens. Suas obras, A Cidade e a Criança (1989 e Arquitetura e Educação (1995 revelam a preocupação com os projetos dos espaços de parques e escolas, principalmente, com os seus usuários.

Venice: a meeting, a plague, a death

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Óscar Botasso

2008-10-01

Full Text Available Death in Venice is based on the novella of the same name by Thomas Mann, except that in the cinema version the main character, Gustav von Aschenbach, is a musician instead of a writer. Owing to poetic license not always within the layman’s grasp, Luchino Visconti also wished to identify the artist with Gustav Mahler. Beyond such dissimilarities, however, the film is a feasible recreation of the story and a faithful reconstruction of those times: a Venice divorced from its former splendor and invaded by a plague and yet at the same time still able to evoke the captivating, nostalgic legacy of its magnificent past. An ideal scenario indeed for the musical ideas of Mahler, and perfectly reflected in the Midnight Song and the adagietto of his third and fifth symphonies.

A retirement and a reservation: a retrospective autobiography.

Science.gov (United States)

Lee, Sok K

2012-01-01

A retirement is a rite of passage that requires careful planning, because it forces a retiree to make a shift in the paradigm in life. For 37 years, I was a healing professional, a breadwinner, and a working spouse. I am now a jobless loner, an inactive pensioner, and a homebound spouse. In this retrospective autobiography, I suggest a few points to help my younger colleagues to better their upcoming retirement: professional, financial, social, and familial. To overcome Erikson's identity crisis, I volunteered to be a wounded healer at Warm Springs Indian Reservation. My volunteer medical service at Warm Springs Indian Reservation was a good antidote to creatively overcome my postretirement blues.

A batuta da morte a orquestrar a vida

Directory of Open Access Journals (Sweden)

Altair Macedo Lahud Loureiro

Full Text Available Com colocações de outros estudiosos da morte, teço e apresento apontamentos rápidos sobre a morte a organizar a vida. Esposo a idéia da necessidade da morte para que a vida tenha sentido nesta busca humana da completude. Endereço o olhar para uma situação especial de relação com a morte: a reação dos que ficam ao presenciar e sentir a morte de um dos seus idosos; daquele familiar, ou não, que assume o seu cuidado e acompanha o seu fim iminente; que presencia, humanamente impotente, a hora da solitária partida. Solitária morte, pois que exclusiva, própria daquele idoso do qual cuidava, do seu fim natural, por ser humano.

A rose is a rose is a rose

NARCIS (Netherlands)

Vinkers, Christiaan H.

2017-01-01

Over a century ago in 1913, the poet Gertrude Stein wrote these famous words: sometimes things are just what they are. There has been a recent debate centred around the question whether or not schizophrenia exists. Is there a brain disease that can be called schizophrenia? What difference does it

A device, a system and a method of encoding a position of an object

DEFF Research Database (Denmark)

2012-01-01

The present invention relates to a device for encoding a position of an object, comprising a first light source; a first collimating element adapted to form first collimated light from the first light source; a carrier adapted to guide light and comprising a first primary light redirecting...... structure and a second primary light redirecting structure; and a detector device for encoding the position of an object with respect to an active area of an encoding plane; wherein the first primary light redirecting structure is adapted to redirect at least a part of a first light beam through the active...

Mapping a Space for a Rhetorical-Cultural Analysis: A Case of a Scientific Proposal

Science.gov (United States)

Dorpenyo, Isidore Kafui

2015-01-01

This article analyzes a proposal submitted to a funding unit in Michigan Technological University by a PhD Forestry student. A rhetorical-cultural approach of the text provides evidence to argue that scientific writing is rooted in a cultural practice that valorizes certain kinds of thought, practices, rituals, and symbols; that a scientist's work…

A game is a game is a game

DEFF Research Database (Denmark)

Jørgensen, Ida Kathrine Hammeleff

2017-01-01

Recently self-referentiality have occurred as a trend among game designers and have also enjoyed sporadic attention in academia. However, in academia, discussions of self-referential games often rest on proceduralist arguments and a too exclusive focus on the game object. This paper draws...... on the typology of meta-pictures developed by art historian J.W.T. Mitchell. Based on this typology, this paper discusses the notion of meta-games and suggest a broad conception of such games that includes not only the game object, but also the player and the discourse in which it is interpreted....

A search for a new gauge boson A'

Energy Technology Data Exchange (ETDEWEB)

Jensen, Eric L. [College of William and Mary, Williamsburg, VA (United States)

2013-08-01

In the Standard Model, gauge bosons mediate the strong, weak, and electromagnetic forces. New forces could have escaped detection only if their mediators are either heavier than order(TeV) or weakly coupled to charged matter. New vector bosons with small coupling {alpha}' arise naturally from a small kinetic mixing with the photon and have received considerable attention as an explanation of various dark matter related anomalies. Such particles can be produced in electron-nucleus fixed-target scattering and then decay to e⁺e^-+ pairs. New light vector bosons and their associated forces are a common feature of Standard Model extensions, but existing constraints are remarkably sparse. The APEX experiment will search for a new vector boson A' with coupling α'/α_fs > 6 × 10^-8 to electrons in the mass range 65MeV < mass A' < 550MeV. The experiment will study e⁺e^- production off an electron beam incident on a high-Z target in Hall A at Jefferson Lab. The e^- and e⁺ will be detected in the High Resolution Spectrometers (HRSs). The invariant mass spectrum of the e⁺e^- pairs will be scanned for a narrow resonance corresponding to the mass of the A'. A test run for the APEX experiment was held in the summer of 2010. Using the test run data, an A' search was performed in the mass range 175-250 MeV. The search found no evidence for an A' → e⁺e^-reaction, and set an upper limit of {alpha}'/{alpha}{sub fs} ~ 10^-6.

VacA, CagA, IceA and OipA Genotype Status of Helicobacter pylori ...

African Journals Online (AJOL)

Purpose: To investigate the state of vacA, cagA, oipA and iceA genotypes of H. pylori isolated from gastric biopsy samples of dogs. Methods: A total of 240 gastric biopsy samples were taken from 240 dogs using gastric endoscope. All the samples were cultured and H. pylori-positive samples were analyzed for the presence ...

A Burger, a Beer, and a Side of Science

Science.gov (United States)

Wiehe, B. R.; Landsberg, R. H.; Wyatt, R. J.; Turner, M. S.

2008-11-01

Science cafés (a.k.a. café scientifiques) engage unconventional adult audiences and help researchers hone their communication skills in a relaxed and fun setting. Typically held in restaurants and pubs, science cafés provide a comfortable place for the public to speak with a scientist. National and local evaluations of the café format indicate that café are an effective way to engage adult audiences (especially non-scientists). Continued media coverage also demonstrates that something about them captures the public's imagination. This paper is based on an interactive oral presentation about organizing, presenting, and partnering with science café to bring IYA themes (and other current research) directly to new audiences. Real world examples from experienced café organizers and presenters provide an overview of what a science café is, how to start one, and how to use the format to draw attention to astronomy topics. The discussion includes suggestions for tapping into the existing national and international community of cafés (there are more than 60 in the U.S. alone), and information about free outreach resources. Break-out exercises in the original oral presentation were designed to help prepare participants to: find a suitable venue, advertise, work with café speakers, and foster the inclusive conversation that is the hallmark of a science café. Participants also learned about the impacts that can be expected from a science café, including benefits to audiences, café presenters, and hosting organizations. The overall goal of the original oral presentation was to stimulate a discussion about strategies for facilitating face-to-face communication between scientists and lay audiences.

A surface containing a line and a circle through each point is a quadric

KAUST Repository

Nilov, Fedor K.; Skopenkov, Mikhail

2012-01-01

We prove that a surface in 3-dimensional Euclidean space containing a line and a circle through each point is a quadric. We also give some particular results on the classification of surfaces containing several circles through each point. © 2012 Springer Science+Business Media B.V.

A surface containing a line and a circle through each point is a quadric

KAUST Repository

Nilov, Fedor K.

2012-06-20

We prove that a surface in 3-dimensional Euclidean space containing a line and a circle through each point is a quadric. We also give some particular results on the classification of surfaces containing several circles through each point. © 2012 Springer Science+Business Media B.V.

A ROBOT AND A METHOD OF CONTROLLING A ROBOT

DEFF Research Database (Denmark)

2017-01-01

The present invention relates to a robot comprising a horizontal or horizontally slanted transparent experiment layer being adapted to support items at arbitrary positions on or in the experiment layer, and a moveable sensor arranged below the transparent experimental layer said sensor being...

S A H A R A J

African Journals Online (AJOL)

(2004). Social, cultural and sexual behavioral determinants of observed decline in .... was given to a life orientation educator at the local high school who was ..... out of perceived invulnerability and imagined biological immunity, based on ...

Eph receptor A10 has a potential as a target for a prostate cancer therapy

International Nuclear Information System (INIS)

Nagano, Kazuya; Yamashita, Takuya; Inoue, Masaki; Higashisaka, Kazuma; Yoshioka, Yasuo; Abe, Yasuhiro; Mukai, Yohei; Kamada, Haruhiko

2014-01-01

Highlights: • EphA10 mRNA is overexpressed in breast, prostate and colon cancer cell lines. • EphA10 is overexpressed in clinical prostate tumors at mRNA and protein levels. • Anti-EphA10 antibodies were cytotoxic on EphA10-positive prostate cancer cells. - Abstract: We recently identified Eph receptor A10 (EphA10) as a novel breast cancer-specific protein. Moreover, we also showed that an in-house developed anti-EphA10 monoclonal antibody (mAb) significantly inhibited proliferation of breast cancer cells, suggesting EphA10 as a promising target for breast cancer therapy. However, the only other known report for EphA10 was its expression in the testis at the mRNA level. Therefore, the potency of EphA10 as a drug target against cancers other than the breast is not known. The expression of EphA10 in a wide variety of cancer cells was studied and the potential of EphA10 as a drug target was evaluated. Screening of EphA10 mRNA expression showed that EphA10 was overexpressed in breast cancer cell lines as well as in prostate and colon cancer cell lines. Thus, we focused on prostate cancers in which EphA10 expression was equivalent to that in breast cancers. As a result, EphA10 expression was clearly shown in clinical prostate tumor tissues as well as in cell lines at the mRNA and protein levels. In order to evaluate the potential of EphA10 as a drug target, we analyzed complement-dependent cytotoxicity effects of anti-EphA10 mAb and found that significant cytotoxicity was mediated by the expression of EphA10. Therefore, the idea was conceived that the overexpression of EphA10 in prostate cancers might have a potential as a target for prostate cancer therapy, and formed the basis for the studies reported here

‘A rose is a rose is a rose’

NARCIS (Netherlands)

Vinkers, C H

2017-01-01

Over a century ago in 1913, the poet Gertrude Stein wrote these famous words: sometimes things are just what they are. There has been a recent debate centred around the question whether or not schizophrenia exists. Is there a brain disease that can be called schizophrenia? What difference does it

S A H A R A J

African Journals Online (AJOL)

The book begins with an outline of the importance of AIDS and its potential to impact on ... qualitative, comprising twenty case studies in which household livelihood ... analysis means that this section provides more of a story than systematic or ...

A Burger, A Beer, and A Side of Science

Science.gov (United States)

Wiehe, Ben; Landsberg, R. H.; Wyatt, R. J.; Turner, M. S.

2008-05-01

Science Cafés (aka Café Scientifiques) engage unconventional adult audiences and help researchers hone their communication skills in a relaxed and fun setting. Typically held in restaurants and pubs, Science Cafés provide a comfortable place for the public to speak with a scientist. National and local evaluations of the Café format indicate that cafes are an effective way to engage adult audiences (especially non-scientists). Continued media coverage also demonstrate that something about them captures the public's imagination. Join us for an interactive session about organizing, presenting and partnering with Science Cafés to bring IYA themes (and other current research) directly to new audiences. Real world examples from experienced Café organizers and presenters will provide an overview of what a Science Café is, how to start one and how to use the format to draw attention to astronomy topics. The discussion will include suggestions for tapping into the existing national and international community of Cafés (there are more than 60 in the US alone), and information about free outreach resources. Break-out exercises will help prepare you to: find a suitable venue, advertise, work with café speakers, and foster the inclusive conversation that is the hallmark of a Science Café. Participants will also learn about the impacts that can be expected from a Science Café including benefits to audiences, Café presenters, and hosting organizations. The overall goal of this session is to stimulate a discussion about strategies for facilitating face-to-face communication between scientists and lay audiences. Participants will have the opportunity to create their own promotional plan for a Café event, including the important process of framing a topic to grab public attention, and developing strategies for reaching new target audiences. Substantial time will be allowed for participants to discuss how the Science Café format might be adapted for their specific

A Project Team: a Team or Just a Group?

Directory of Open Access Journals (Sweden)

Kateřina

2014-06-01

Full Text Available This paper deals with issues related to work in either teams or groups. The theoretical part discusses a team and a group with regards to its definition, classification and basic distinction, brings in more on the typology of team roles, personality assessment and sociometric methods. The analytical part tests the project (work team of a medical center represented in terms of personality and motivational types, team roles and interpersonal team relations concerning the willingness of cooperation and communication. The main objective of this work is to verify the validity of the assumptions that the analyzed team represents a very disparate group as for its composition from the perspective of personality types, types of motivation, team roles and interpersonal relations in terms of the willingness of cooperation and communication. A separate output shall focus on sociometric investigation of those team members where willingness to work together and communicate is based on the authors’ assumption of tight interdependence.

A Project Team: A Team or Just a Group?

Directory of Open Access Journals (Sweden)

Katerina Hrazdilova Bockova

2013-11-01

Full Text Available This paper deals with issues related to work in either teams or groups. The theoretical part which discusses a team and a group with regards to its definition, classification and basic distinction brings in more on the typology of team roles, personality assessment and sociometric methods. The analytical part tests the project (work team of a medical center represented in terms of personality and motivational types, team roles and interpersonal team relations concerning the willingness of cooperation and communication. The main objective of this work was to determine whether the existing team is not by its nature rather a working group that contributes to the generally perceived stagnation of that field.

Medusa spectroscopy of A400, A576, A1767, and A2124

International Nuclear Information System (INIS)

Hintzen, P.; Hill, J.M.; Lindley, D.; Scott, J.S.; Angel, J.R.P.

1982-01-01

Galaxy velocity data taken with the Steward Observatory multiple aperture fiber optic spectrograph are presented for four Abell clusters. The root-mean-square external errors in these velocities are about 100 km/s; accuracy which compares favorably with that obtained from single-object observations. We expect that the recent adoption of a CCD detector should decrease external errors to about 50 km/s. All four of the clusters observed are known x-ray sources and our data agree well with empirically derived velocity dispersion--x-ray luminosity relations for clusters of galaxies. Abell 400 is interesting in this regard, since both its x-ray luminosity and its velocity dispersion are quite small. Such objects are particularly important in determining the slope of the velocity dispersion--x-ray luminosity relation. The large microwave decrement observed in A576 was initially interpreted as due to Compton scattering of the microwave background by the x-ray-emitting intracluster gas. White and Silk have presented Einstein x-ray data which indicate that A576 contains too little gas to produce the observed microwave decrement by Compton scattering. Our velocity dispersion for 47 members of this cluster strengthens their conclusion

Medusa spectroscopy of A400, A576, A1767, and A2124

Science.gov (United States)

Hintzen, P.; Hill, J. M.; Lindley, D.; Scott, J. S.; Angel, J. R. P.

1982-01-01

Galaxy velocity data taken with the Steward Observatory multiple aperture fiber optic spectrograph are presented for four Abell clusters. The root-mean-square external errors in these velocities are about 100 km/s; accuracy which compares favorably with that obtained from single-object observations. It is expected that the recent adoption of a CCD detector should decrease external errors to about 50 km/s. All four of the clusters observed are known X-ray sources and the present data agree well with empirically derived velocity dispersion-X-ray luminosity relations for clusters of galaxies. Abell 400 is interesting in this regard, since both its X-ray luminosity and its velocity dispersion are quite small. Such objects are particularly important in determining the slope of the velocity dispersion-X-ray luminosity relation. The large microwave decrement observed in A576 was initially interpreted as due to Compton scattering of the microwave background by the X-ray-emitting intracluster gas. White and Silk have presented Einstein X-ray data which indicate that A576 contains too little gas to produce the observed microwave decrement by Compton scattering. The velocity dispersion obtained here for 47 members of this cluster strengthens their conclusion.

Improving Photovoltaic Performance of a Fused-Ring Azepinedione Copolymer via a D-A-A Design.

Science.gov (United States)

Zhang, Honghong; Li, Ting; Xiao, Zuo; Lei, Zhongli; Ding, Liming

2018-04-01

Two conjugated copolymer donors, PTTABDT and PBTTABDT, based on a fused-ring azepinedione acceptor unit, 5-(2-octyldodecyl)-4H-thieno[2',3':4,5]thieno[3,2-c]thieno[2',3':4,5]thieno[2,3-e]azepine-4,6(5H)-dione (TTA), are prepared. PTTABDT possesses a conventional donor-acceptor (D-A) structure with one TTA in the repeat unit, while PBTTABDT has a D-A-A structure with two TTAs in the repeat unit. Compared with PTTABDT, PBTTABDT shows a deeper highest occupied molecular orbital (HOMO) level, a narrower bandgap, and a higher hole mobility, and exhibits better performance in bulk heterojunction solar cells. Power conversion efficiencies of 6.18% and 7.81% are achieved from PTTABDT:PC 71 BM and PBTTABDT:PC 71 BM solar cells, respectively. The higher performance of PBTTABDT:PC 71 BM solar cells results from the enhanced open-circuit voltage (V oc ) and short-circuit current density (  J sc ). © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Aspirina e a Asma

Directory of Open Access Journals (Sweden)

K.S. Babu

2001-03-01

Full Text Available RESUMO: A aspirina é não só o fannaco me1hor estudado em todo o mundo, como o mais frequentemente uti1izado em todos os tempos. Alem das suas propriedades como analgesico e antipiretico, o acido acetilsalicflico (AAS e urn inibidor da agregação plaquetária, o que the confere urn papel essencial na profilaxia do tromboembolismo e na prevenção dos acidentes cardio e cerebro-vasculares.A associação da sensibilidade á aspirina, com a asma e a polipose nasal, descrita pela primeira vez por Femand Widal e colaboradores, constitui a trfade da “Asma lnduzida pela Aspirina” (AlA e refere-se ao desenvolvimento de urn quadro de broncoconstrição em indivfduos asmaticos após ingestao de aspirina. Nestes doentes, os sintomas agudos sobrepõem-se ao quadro clfnico de asma crónica grave. As crises de asma podem ser desencadeadas por pequenas quantidades de AAS ou de outros anti-inflamatórios nao ester6ides (AINE’ s.A prevalência da AIA na comunidade é incerta, mas os doentes com AIA constituem 10 a 20% da popula9ao asmatica, sendo a AIA mais frequente nas mulheres. Os autores deste trabalho fazem uma revisão teórica da AIA, descrevendo a apresentação clfnica, os mecanismos patogenicos, o diagnóstico e o tratamento deste síndrome.A asma e uma doença inflamatória crónica das vias aéreas. Neste estado de inflamação continua, a exposiyao aaspirina provoca no subgrupo de doentes com AIA uma acentuayao temporaria do processo inflamat6rio, que conduz á exacerbayao da asma. Embora assemelhando-se as reacçães de hipersensibilidade imediata, a AIA nao parece ser mediada por mecanismos dependentes da IgE, daí estas reacçães scrcm dcsignadas de “anafilactóides”.A hipersensibilidade à aspirina parece antes ser mediada por um desvio da via metab6lica do acido araquidónico no sentido da produção excessiva de leucotrienos, por

A Demonstration and a Souvenir

Science.gov (United States)

Lentz, Randy

1978-01-01

Describes an activity using interchangeable, preset tool holders to provide a demonstration for parents or students attending a school's open house session that produces a small souvenir (an aluminum mini-chalice) for them. A procedure sheet for the school's individual lathe and specification diagrams for making the cup are provided. (TA)

A design of a first wall for a demo reactor

International Nuclear Information System (INIS)

Bond, A.; Bond, R.A.; Cooke, P.I.H.

1985-01-01

A design of a first wall for a Demonstration reactor is reported based on an analysis of heat trasnport, sputtering damage, blanket neutronics and vacuum characteristics. The design comprises replaceable tungsten tiles radiatively cooled to a copper substrate, which in turn is cooled by high pressure helium. The overall engineering design of the first wall is described together with a discussion of the factors influencing the choice of design and materials

A system extinguishing a fire by insulating a liquid fuel

International Nuclear Information System (INIS)

Colome, Jacques; Duchene, Alain; Regnier, Jean.

1975-01-01

The invention refers to a system for quickly extinguishing a liquid fuel body on fire by insulating it completely from the ambient air. It applies particularly to the case of a high temperature liquid sodium sheet flowing accidentally from a circuit belonging to a fast neutron reactor. The system in question includes a lower receptacle for collecting the liquid fuel and a top cover shutting off the receptacle. This cover has inclined channels to take the liquid fuel flow and openings to allow this liquid through at the bottom end of the channels. These openings are closed by retractable shutters moving away under the pressure of the liquid in the channels and closing automatically after the liquid has flowed into the receptacle [fr

A cabeça voraz

Directory of Open Access Journals (Sweden)

Betty Mindlin

1996-08-01

Full Text Available o artigo focaliza um mito indígena sobre a cabeça voadora e voraz, registrado pela autora em vários grupos indígenas da Amazônia, como os Tupari, os Macurap, os Jabuti, os Aruá, os Sateré-Mawé. Cada versão do mito tem um enredo diferente, mas o tema intrigante é sempre o mesmo: a mutilação do corpo, a cabeça que se transforma ou cola-se num outro ser. Procura-se mergulhar no significado desse mito, ao qual Claude Lévi-Strauss dedicou boa parte de dois livros magistrais, A origem das maneiras da mesa e A oleira ciumenta, e que foi usado por Mário de Andrade no livro clássico sobre o herói brasileiro, Macunaína, uma das poucas obras de fição brasileira a se inspirar em temas e personagens míticos indígenas. O registro de campo desse mito é uma pequena ponta de um amplo trabalho de documentação da tradição e dos mitos indígenas brasileiros, que a autora vem realizando há alguns anos. A intenção, nesse texto, é compreender a riqueza do imaginário indígena brasileiro, insistir na necessidade de documentar culturas que são nossas contemporâneas e ainda bastante desconhecidas. A fição e a arte brasileiras poderiam ampliar muito o seu universo ao explorar e tentar compreender as raízes brasileiras que nos são dadas por mais de 200 povos indígenas do país. Também para os índios, escrever, contar, divulgar e usar nas próprias escolas os seus mitos é importante para reafirmar a identidade étnica e valorizar sua participação na sociedade brasileira.The article focuses an indian myth about a flying and voracious head, that was told to the author by several indian tribes from the Amazon, such as the Tupari, the Macurap, the Jabuti, the Aruá, the Sateré-Mawé. Each version has a different plot, but the intriguing theme is always the same: the mutilation of the body, a head that is transformed or attaches itself to another being. The essay delves into the meaning of this myth, to which Claude L�

Entre a literatura e a filosofia: a intertextualidade nassariana

Directory of Open Access Journals (Sweden)

Maria Aparecida Antunes de Macedo

2009-01-01

Full Text Available O romance Lavoura arcaica, de Raduan Nassar, insere-se nas tendências dapós-modernidade filosófica e do pós-modernismo artístico, na medida em quenele se encontra uma poética intertextual apontando tanto para a crítica à razãouniversal do Iluminismo quanto para a problematização do homem no discurso– aspectos centrais nas teorias pós-modernas. Em Cadernos de literaturabrasileira: Raduan Nassar, o escritor situa sua poética na flutuação de doisdomínios do conhecimento, que são a literatura e a filosofia – esta última sendogeradora de seu trabalho intertextual. Em seu texto ficcional, entrevemos essapoética nos comentários autoteorizantes efetuados pelo narrador, em suaaproximação paralela à crítica da pós-modernidade.

A Psychological Factor Affecting a Cardiac Condition in a Psychotherapist

OpenAIRE

R Waxman; K Khorasani; A Lenny; S Bhalerao

2009-01-01

It has been established that intense emotions can affect the development and course of cardiac arrhythmias. This study sought to convey that a lack of expression of emotion can also have an effect on arrhythmias. A psychotherapist with Idiopathic Ventricular Fibrillation and an Implantable Cardioverter Defibrillator measured his rate of Premature Ventricular Contractions using a Holter monitor during three separate six-week periods and in three domains: A) work days vs. off days, B) a 27 hour...

A psychological profile of a serial killer: a case report.

Science.gov (United States)

Dogra, T D; Leenaars, Antoon A; Chadha, R K; Manju, Mehta; Lalwani, Sanjeev; Sood, Mamta; Lester, David; Raina, Anupuma; Behera, C

2012-01-01

Serial killers have always fascinated society. A serial killer is typically defined as a perpetrator who murders three or more people over a period of time. Most reported cases of serial killers come from the United States and Canada. In India, there are few reported cases. We present, to the best of our knowledge, the first Indian case in the literature. The present case is of a 28-year-old man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences, New Delphi handled the forensic study. We present a most unique psychological investigation into the mind of a serial killer.

A Pulsar and a Disk

Science.gov (United States)

Kohler, Susanna

2016-07-01

Recent, unusual X-ray observations from our galactic neighbor, the Small Magellanic Cloud, have led to an interesting model for SXP 214, a pulsar in a binary star system.Artists illustration of the magnetic field lines of a pulsar, a highly magnetized, rotating neutron star. [NASA]An Intriguing BinaryAn X-ray pulsar is a magnetized, rotating neutron star in a binary system with a stellar companion. Material is fed from the companion onto the neutron star, channeled by the objects magnetic fields onto a hotspot thats millions of degrees. This hotspot rotating past our line of sight is what produces the pulsations that we observe from X-ray pulsars.Located in the Small Magellanic Cloud, SXP 214 is a transient X-ray pulsar in a binary with a Be-type star. This star is spinning so quickly that material is thrown off of it to form a circumstellar disk.Recently, a team of authors led by JaeSub Hong (Harvard-Smithsonian Center for Astrophysics) have presented new Chandra X-ray observations of SXP 214, tracking it for 50 ks (~14 hours) in January 2013. These observations reveal some very unexpected behavior for this pulsar.X-ray PuzzleThe energy distribution of the X-ray emission from SXP 214 over time. Dark shades or blue colors indicate high counts, and light shades or yellow colors indicate low counts. Lower-energy X-ray emission appeared only later, after about 20 ks. [Hong et al. 2016]Three interesting pieces of information came from the Chandra observations:SXP 214s rotation period was measured to be 211.5 s an increase in the spin rate since the discovery measurement of a 214-second period. Pulsars usually spin down as they lose angular momentum over time so what caused this one to spin up?Its overall X-ray luminosity steadily increased over the 50 ks of observations.Its spectrum became gradually softer (lower energy) over time; in the first 20 ks, the spectrum only consisted of hard X-ray photons above 3 keV, but after 20 ks, softer X-ray photons below 2 ke

When is a theory a theory? A case example.

Science.gov (United States)

Alkin, Marvin C

2017-08-01

This discussion comments on the approximately 20years history of writings on the prescriptive theory called Empowerment Evaluation. To do so, involves examining how "Empowerment Evaluation Theory" has been defined at various points of time (particularly 1996 and now in 2015). Defining a theory is different from judging the success of a theory. This latter topic has been addressed elsewhere by Michael Scriven, Michael Patton, and Brad Cousins. I am initially guided by the work of Robin Miller (2010) who has written on the issue of how to judge the success of a theory. In doing so, she provided potential standards for judging the adequacy of theories. My task is not judging the adequacy or success of the Empowerment Evaluation prescriptive theory in practice, but determining how well the theory is delineated. That is, to what extent do the writings qualify as a prescriptive theory. Copyright © 2016 Elsevier Ltd. All rights reserved.

A contabilidade a valor justo e a crise financeira mundial

OpenAIRE

Eric Barreto de Oliveira

2009-01-01

A contabilidade a valor justo tem sido discutida desde meados do século passado; porém, tomou força maior a partir de publicações recentes do FASB (Financial Accounting Standards Board) e do IASB (International Accounting Standards Board). Mais recentemente, em resposta à crise global de 2008, inicialmente chamada de crise do subprime, a SEC (Securities Exchange Comission), o FASB e o IASB rediscutiram exaustivamente este critério de mensuração, com o objetivo de detectar falhas que poderiam ...

The information a history, a theory, a flood

CERN Document Server

Gleick, James

2011-01-01

Winner of the Royal Society Winton Prize for Science Books 2012, the world's leading prize for popular science writing. We live in the information age. But every era of history has had its own information revolution: the invention of writing, the composition of dictionaries, the creation of the charts that made navigation possible, the discovery of the electronic signal, the cracking of the genetic code. In 'The Information' James Gleick tells the story of how human beings use, transmit and keep what they know. From African talking drums to Wikipedia, from Morse code to the 'bit', it is a fascinating account of the modern age's defining idea and a brilliant exploration of how information has revolutionised our lives.

Can a String's Tension Exert a Torque on a Pulley?

Science.gov (United States)

Krause, Dennis E.; Sun, Yifei

2011-01-01

A typical textbook problem in rotational dynamics involves calculating the angular acceleration of a massive pulley due to a string, such as in the example shown in Fig. 1. The string is assumed to be massless and to move without slipping over the pulley, which is mounted on a frictionless axle. If T[subscript L] and T[subscript R] are the…

[Caffeine: a nutrient, a drug or a drug of abuse].

Science.gov (United States)

Pardo Lozano, Ricardo; Alvarez García, Yolanda; Barral Tafalla, Diego; Farré Albaladejo, Magí

2007-01-01

Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

Criança: objeto a liberado? Child: freed object a?

Directory of Open Access Journals (Sweden)

Glaucineia Gomes de Lima

2009-04-01

Full Text Available Lacan (1968-69 abordou a criança como objeto a liberado. Assim, ela é capturada no gozo, drama em torno do qual a família se estrutura. Tais formulações são questionadas no texto que discute o lugar da criança como objeto de gozo nos tempos atuais. Parte-se da discussão sobre a sociedade da globalização, cuja lógica se orienta para a produção incessante de objetos de consumo, marcada pelo declínio dos ideais e o impulso ao hedonismo mortífero. O imperativo do consumo na sociedade globalizada não é sem conseqüências para a educação, que se guia pela lógica de educar para o mercado, empreitada que tem como efeito o fracasso escolar, um dos nomes do 'mal-estar' na educação. Desponta, entre educadores e educandos, apatia, tédio e indiferença no vazio em que parece ter se tornado o espaço escolar. Os efeitos de retorno do gozo incidem sobre o corpo das crianças, que é objeto de maus-tratos, violência, pedofilia e todo tipo de abusos. Assim, conclui-se questionando qual é o lugar para a escuta do sintoma, face ao imperativo de consumo e a ascensão do objeto, e as suas conseqüências para o apagamento da subjetividade da criança.Lacan approached the child as a freed object a. Thus, the child is captured in pleasure, drama upon which family is structured. These formulations are questioned in the text that approaches child as the current object of pleasure. The departing point is the discussion on the globalized society which heads to the on-going production of consumer objects, labeled by the decay of ideals and its drive to a lethal hedonism. But the consumption imperative in the globalized society has its own consequences on education which entails the logic of instructing for the market, leading to an educational failure, also known as educational uneasiness. What emerges from educators and students is apathy, boredom and indifference in the emptiness that schools seem to have turned into. The results of the return

A-THREE: a user's manual

International Nuclear Information System (INIS)

Auerbach, E.H.

1977-06-01

A-THREE is an optical-model code for elastic scattering, specifically designed for the requirements of heavy-ion projectiles. Fast search procedures for fitting model parameters to experimental data are provided. Because of structural similarity, provision for bound-state calculation is also included. In a sense, this code is ''grandson of ABACUS-2;'' it has, however, been written completely anew. Principal features include the ability to calculate to high partial waves (up to l = 800), refinement of integration meshes for large wave number, and a variety of forms for the optical potentials. The very superior Manchester Coulomb Wave Functions Routine, good in all parts of the (rho, eta) plane is used. This code, written in Fortran-extended, has been in use at Brookhaven on its CDC-7600 for the last two years, during which a number of minor improvements have been added. A general overview of the principal features of the code is given first, with some recommendations for input. This overview is intended to guide the user, and is not intended as a detailed description of the code. Then follow sections describing the input cards and the output generated by the code. These sections are sufficiently detailed to permit a user to prepare input without reference to a code listing. Finally, material necessary for writing special potential well subroutines and tables of control and parameter numbers are appended

María Zambrano: a woman, a republican and a philosopher in exile

Directory of Open Access Journals (Sweden)

PATRICIA PALOMAR GALDÓN

2013-09-01

Full Text Available The subject of this presentation is an attempt to understand the concept of exile in terms of the works of Spanish philosopher María Zambrano, a woman who left her country after the Spanish civil war and lived the life of an exile. This work focuses on the difficulties encountered by thinkers when they try to reflect on the experience of exile, and it aims to bring Zambrano’s thought on exile closer to her main philosophical concepts.

The collision of a strong shock with a gas cloud: a model for Cassiopeia A

International Nuclear Information System (INIS)

Sgro, A.G.

1975-01-01

The result of the collision of the shock with the cloud is a shock traveling around the cloud, a shock transmitted into the cloud, and a shock reflected from the cloud. By equating the cooling time of the posttransmitted shock gas to the time required for the transmitted shock to travel the length of the cloud, a critical cloud density n/subc/ /sup prime/ is defined. For clouds with density greater than n/subc/ /sup prime/, the posttransmitted shock gas cools rapidly and then emits the lines of the lower ionization stages of its constituent elements. The structure of such and its expected appearance to an observer are discussed and compared with the quasi-stationary condensations of Cas A. Conversely, clouds with density less than n/subc//sup prime/ remain hot for several thousand years, and are sources of X-radiation whose temperatures are much less than that of the intercloud gas. After the transmitted shock passes, the cloud pressure is greater than the pressure in the surrounding gas, causing the cloud to expand and the emission to decrease from its value just after the collision. A model in which the soft X-radiation of Cas A is due to a collection of such clouds is discussed. The faint emission patches to the north of Cas A are interpreted as preshocked clouds which will probably become quasi-stationary condensations after being hit by the shock

A patient with a painless neck tumour revealed as a carotid paraganglioma: a case report.

Science.gov (United States)

Peric, Barbara; Marinsek, Ziva Pohar; Skrbinc, Breda; Music, Maja; Zagar, Ivana; Hocevar, Marko

2014-08-20

Carotid paragangliomas are usually slowly enlarging and painless lateral neck masses. These mostly benign lesions are recognized due to their typical location, vessel displacement and specific blood supply, features that are usually seen on different imaging modalities. Surgery for carotid paraganglioma can be associated with immediate cerebrovascular complications or delayed neurological impairment.We are reporting the case of a 36-year-old man who presented with a painless mass on the right side of his neck 11 months after being treated for testicular cancer. After a fine-needle aspiration biopsy, he was diagnosed with a testicular cancer lymph node metastasis. Neck US and fluorine [F-18]-fluorodeoxy-D-glucose (FDG) PET-CT showed no signs of hypervascularity or vessel displacement. The patient underwent a level II to V functional neck dissection. During the procedure, suspicion of a carotid paraganglioma was raised and the tumour was carefully dissected from the walls of the carotid arteries with minimal blood loss and no cranial nerve dysfunction.The histology report revealed carotid paraganglioma with no metastasis in the rest of the lymph nodes. The patient's history of testicular germ cell tumour led to a functional neck dissection during which a previously unrecognized carotid paraganglioma was removed.Surgery for carotid PG can be associated with complications that have major impact on quality of life. A thorough assessment of the patient and neck mass must therefore be performed preoperatively in order to perform the surgical procedure under optimal conditions.

On a question of A. Balog

OpenAIRE

Shkredov, Ilya D.

2015-01-01

We give a partial answer to a conjecture of A. Balog, concerning the size of AA+A, where A is a finite subset of real numbers. Also, we prove several new results on the cardinality of A:A+A, AA+AA and A:A + A:A.

A method of providing a barrier in a fracture-containing system

DEFF Research Database (Denmark)

2014-01-01

The present invention relates to a method of providing a barrier in a fracture-containing system, comprising: i) Providing a treatment fluid comprising: a) a base fluid; b) an elastomeric material, wherein said elastomeric material comprises at least one polymer capable of crosslinking into an el......The present invention relates to a method of providing a barrier in a fracture-containing system, comprising: i) Providing a treatment fluid comprising: a) a base fluid; b) an elastomeric material, wherein said elastomeric material comprises at least one polymer capable of crosslinking...... into an elastomer, and c) at least one crosslinking agent; ii) Placing the treatment fluid in a fracture-containing system; iii) Allowing the elastomeric material to crosslink with itself to form a barrier in said fracture-containing system; wherein the elastomeric material and/or the crosslinking agent...... are of neutral buoyancy with regard to the base fluid. The invention is contemplated to having utility not only in the oil-drilling industry but also in the plugging of fractures in sewer drains, pipelines etc....

A Psychological Factor Affecting a Cardiac Condition in a Psychotherapist

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R Waxman

2009-03-01

Full Text Available It has been established that intense emotions can affect the development and course of cardiac arrhythmias. This study sought to convey that a lack of expression of emotion can also have an effect on arrhythmias. A psychotherapist with Idiopathic Ventricular Fibrillation and an Implantable Cardioverter Defibrillator measured his rate of Premature Ventricular Contractions using a Holter monitor during three separate six-week periods and in three domains: A work days vs. off days, B a 27 hour work week vs. 22 hour work week, and C in 5 different modalities including 1 Meeting with department head 2 Individual psychotherapy with patients 3 Group therapy with patients 4 Supervision of residents 5 Personal psychoanalysis. The results showed more than a 3-fold increase of arrhythmogenic activity during the 27-hour work week vs. 22 and a 5-fold increase in arrhythmogenic activity on work days compared to days off. Department Head meetings were found to be most arrhythmogenic and personal psychoanalysis was least. The data suggest that the psychiatrist’s lack of emotional expression in his clinical work has been demonstrated to markedly worsen his arrhythmia. The results also point to the potential ameliorating effects of the therapist’s own psychotherapy.

A quackery with a difference

DEFF Research Database (Denmark)

Wahlberg, Ayo

2007-01-01

in which regulatory authorities in the UK have come to address what is invariably described as a ‘growing interest in CAM’, I will show how the problem of quackery today is increasingly located in an ethical field of practitioner competency, qualifications, conduct, responsibility and personal professional...... health. Yet, in this paper, I argue that this is only one form that the problem of ‘quackery’ has taken in the past two centuries or so in the United Kingdom. Just as Roy Porter showed how the mid-19th century professionalization of medicine gave rise to a ‘quackery with a difference’ as a whole range...

A.A., constructivism, and reflecting teams.

Science.gov (United States)

Nevels, B

1997-12-01

Numerous studies and clinical anecdotes reveal a relationship between attendance at A.A. meetings and/or degree of involvement in A.A. and maintenance of sobriety. Hypotheses as to how A.A. and/or the A.A. meeting is helpful to its members have ranged from a focus on factors common to all therapy groups, to aspects of A.A. "treatment" which are behavioral in nature. Presented here is another way of understanding A.A.'s effectiveness within the frame of more recent, constructivistic approaches to family therapy. In particular, the A.A. topic meeting is compared to the reflecting team concept of Tom Anderson.

Evidence of a rolling motion of a microparticle on a silicon wafer in a liquid environment

Energy Technology Data Exchange (ETDEWEB)

Schiwek, Simon; Stark, Robert W., E-mail: stark@csi.tu-darmstadt.de, E-mail: dietz@csi.tu-darmstadt.de; Dietz, Christian, E-mail: stark@csi.tu-darmstadt.de, E-mail: dietz@csi.tu-darmstadt.de [Physics of Surfaces, Center of Smart Interfaces and Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); Meckel, Tobias [Membrane Dynamics, Department of Biology, Technische Universität Darmstadt, Schnittspahnstrasse 3, 64287 Darmstadt (Germany)

2016-05-21

The interaction of micro- and nanometer-sized particles with surfaces plays a crucial role when small-scale structures are built in a bottom-up approach or structured surfaces are cleaned in the semiconductor industry. For a reliable quantification of the interaction between individual particles and a specific surface, however, the motion type of the particle must be known. We developed an approach to unambiguously distinguish between sliding and rolling particles. To this end, fluorescent particles were partially bleached in a confocal laser scanning microscope to tailor an optical inhomogeneity, which allowed for the identification of the characteristic motion pattern. For the manipulation, the water flow generated by a fast moving cantilever-tip of an atomic force microscope enabled the contactless pushing of the particle. We thus experimentally evidenced a rolling motion of a micrometer-sized particle directly with a fluorescence microscope. A similar approach could help to discriminate between rolling and sliding particles in liquid flows of microfluidic systems.

A Proposal for a Mindset of a Project Manager

DEFF Research Database (Denmark)

Eriksson, Joakim; Hansen, Claus Thorp

2008-01-01

and clarification of decision situations and consequences is rarely used in practice and structured reasoning about project and product performance when making decisions is also rare. In order to enhance the project managers’ understanding of decision-making in product development projects, the objective......A company’s product strategy and its management of the product development process have been found to be key factors for a product’s success on the market [1]. Project managers of development projects need support to make process decisions and defining goals that are consistent with the business....... In product development projects it is desirable to reduce the level of uncertainty in order to make decisions without having to redo them later in the project resulting in longer lead time and higher costs. It is the project manager’s responsibility to manage this uncertainty in a complex ever...

A Hair & a Fungus: Showing Kids the Size of a Microbe

Science.gov (United States)

Richter, Dana L.

2013-01-01

A simple method is presented to show kids the size of a microbe--a fungus hypha--compared to a human hair. Common household items are used to make sterile medium on a stove or hotplate, which is dispensed in the cells of a weekly plastic pill box. Mold fungi can be easily and safely grown on the medium from the classroom environment. A microscope…

A stage is a stage is a stage: a direct comparison of two scoring systems.

Science.gov (United States)

Dawson, Theo L

2003-09-01

L. Kohlberg (1969) argued that his moral stages captured a developmental sequence specific to the moral domain. To explore that contention, the author compared stage assignments obtained with the Standard Issue Scoring System (A. Colby & L. Kohlberg, 1987a, 1987b) and those obtained with a generalized content-independent stage-scoring system called the Hierarchical Complexity Scoring System (T. L. Dawson, 2002a), on 637 moral judgment interviews (participants' ages ranged from 5 to 86 years). The correlation between stage scores produced with the 2 systems was .88. Although standard issue scoring and hierarchical complexity scoring often awarded different scores up to Kohlberg's Moral Stage 2/3, from his Moral Stage 3 onward, scores awarded with the two systems predominantly agreed. The author explores the implications for developmental research.

A Study on a Numerical Modeling of a Friction Pendulum System

International Nuclear Information System (INIS)

Kim, Min Kyu; Choun, Young Sun; Ohtori, Yasuki

2006-01-01

A Friction Pendulum System (FPS) is a well known seismic isolation system. In the case of FPS, the period of a vibration only depends on a radius of a curvature and the gravitational constant, and it does not depend on the mass. For this reason, the FPS is useful for smaller weight equipment and a liquid storage tank which changes its' liquid level. Kim et al. (2004) studied the seismic isolation effect of small equipment by using a natural rubber bearing (NRB), a high damping rubber bearing (HDRB) and a Friction pendulum system (FPS) by an experimental research. In this study, modified Mokha model for a small FPS system was proposed and it was revealed this model matched the experimental results well

Converting a Monopole Emission into a Dipole Using a Subwavelength Structure

Science.gov (United States)

Fan, Xu-Dong; Zhu, Yi-Fan; Liang, Bin; Cheng, Jian-chun; Zhang, Likun

2018-03-01

High-efficiency emission of multipoles is unachievable by a source much smaller than the wavelength, preventing compact acoustic devices for generating directional sound beams. Here, we present a primary scheme towards solving this problem by numerically and experimentally enclosing a monopole sound source in a structure with a dimension of around 1 /10 sound wavelength to emit a dipolar field. The radiated sound power is found to be more than twice that of a bare dipole. Our study of efficient emission of directional low-frequency sound from a monopole source in a subwavelength space may have applications such as focused ultrasound for imaging, directional underwater sound beams, miniaturized sonar, etc.

Biodiesel: A fuel, a lubricant, and a solvent

Science.gov (United States)

Biodiesel is well-known as a biogenic alternative to conventional diesel fuel derived from petroleum. It is produced from feedstocks such as plant oils consisting largely of triacylglycerols through transesterification with an alcohol such as methanol. The properties of biodiesel are largely compet...

A Leitura e a Tela

Directory of Open Access Journals (Sweden)

Sérgio Luiz Alves da Rocha

2015-09-01

  ABSTRACT This paper is a result of a doctoral research, in a public high school in Rio de Janeiro. The main objective of this work was to discuss - with teachers and students - some topics related to their conceptions and practices about reading, throughout pictures that were taken by them during the research. The different ideas about reading, the link between literary reading and other kinds of reading with "new technologies", the function of school, motivating - or not - the access to different places of reading, were some of the topics discussed throughout the research. During the research I analyzed reading as a cultural practice, as proposed by cultural history. The present text emphasizes a part of this discussion focusing on the relationship between image, reading and the school. Keywords: Lecture; Youth; Image; School; Television. RESUMEN Este trabajo es el resultado de una investigación doctoral , en una escuela secundaria pública en Río de Janeiro. El principal objetivo de este trabajo fue discutir - con maestros y estudiantes - algunos temas relacionados con sus concepciones y prácticas acerca de la lectura , a lo largo de las imágenes que fueron tomadas por ellos durante la investigación. Las diferentes ideas acerca de la lectura, la relación entre la lectura literaria y otros tipos de lectura con "nuevas tecnologías", la función de la escuela, motivando - o no - el acceso a los diferentes lugares de lectura, fueron algunos de los temas tratados a lo largo de la investigación. Durante la investigación la lectura fue tratada como práctica cultural, según lo propuesto por la historia cultural. El presente texto hace trata de una parte de esta discusión que se centra en la relación entre la imagen, la lectura y la escuela . Palabras Clave: Lectura; Juventud; Imagen; Escuela; Televisión.   Referências ADORNO, T.W. ; HORKHEIMER, M. A indústria cultural: o esclarecimento como mistificação das massas. In ______. Dialética do

A person in a closed environment as a psychological problem

Directory of Open Access Journals (Sweden)

YuliyaV. Klochko

2013-12-01

Full Text Available This article addresses an ethically weighted problem which is related to modern psychology: when a person lives in a closed environment. A new approach to solving this problem is being examined. It is based on the finding of substantial new functional aspects of the cognitive processes of making and losing meaning. The study of this sub-discipline started with O.K. Tikhomirov’s theory of thinking. The phenomenon of “adaptability to changes in lifestyle” is being analyzed. The substantial characteristics of the notion of a “closed environment” as well as the psychological manifestations which appear when one is forced to live in a closed environment or choses to live in one of his or her own volition are being revealed. According to the author, the new approach will allow us to come closer to understanding and being able to explain the psychological mechanisms of the mental upheaval which prisoners in solitary confinement experience.

A Message Without a Code?

Directory of Open Access Journals (Sweden)

Tom Conley

1981-01-01

Full Text Available The photographic paradox is said to be that of a message without a code, a communication lacking a relay or gap essential to the process of communication. Tracing the recurrence of Barthes's definition in the essays included in Image/Music/Text and in La Chambre claire , this paper argues that Barthes's definition is platonic in its will to dematerialize the troubling — graphic — immediacy of the photograph. He writes of the image in order to flee its signature. As a function of media, his categories are written in order to be insufficient and inadequate; to maintain an ineluctable difference between language heard and letters seen; to protect an idiom of loss which the photograph disallows. The article studies the strategies of his definition in «The Photographic Paradox» as instrument of abstraction, opposes the notion of code, in an aural sense, to audio-visual markers of closed relay in advertising, and critiques the layout and order of La Chambre claire in respect to Barthes's ideology of absence.

A Stroke Mimic: A Case Report

Directory of Open Access Journals (Sweden)

Annia Martínez Rivas

2016-03-01

Full Text Available Diseases mimicking a stroke are a major health problem for a large number of hospitals. This paper aims at presenting a disease that has a stroke-like presentation. The case of a 46-year-old man admitted to the stroke unit with a clinical and radiological diagnosis of cerebral infarction is presented. The patient developed fever and a serious deterioration of consciousness. Changes on computed tomography consistent with a brain abscess were observed. Broad-spectrum antibiotics were administered and a follow-up tomography was performed. Once the treatment was completed, the clinical and radiological suspicion of a brain abscess was confirmed.

Hypernasality in a Shona child with a cleft palate: A phonological ...

African Journals Online (AJOL)

Individuals with hypernasality produce oral sounds with a nasal resonance because of the existence of a cleft palate. This phenomenon has been considered from a number of perspectives, but this article is a description of a phonemic inventory of oral speech sounds produced as nasal sounds by the child under study.

Preguntas a la teología desde la filosofía

Directory of Open Access Journals (Sweden)

Luis Mariano de la Maza

2002-01-01

Full Text Available RESUMEN Se pregunta por los presupuestos que permiten comprender en los tiempos actuales la relación entre la teología y la filosofía, desde la óptica de un creyente. Se parte de una tipificación de seis figuras o formas posibles de entender la relación entre ambas disciplinas: 1 la figura de la identidad, según la cual la filosofía de un cristiano sería indiscernible de la teología; 2 la figura de la diferencia, para la cual filosofía y teología serían disciplinas inconmensurables; 3 la figura del influjo, que enfatiza el condicionamiento mutuo de la filosofía y la teología desde un punto de vista histórico-existencial; 4 la figura de la subordinación, que defiende la tesis de que la filosofía solo alcanza su objetivo con ayuda de la teología; 5 la figura de la oposición, que advierte una amenaza recíproca entre la filosofía y la teología; y finalmente 6 la figura del diálogo, sostenida por el propio autor del artículo, y según la cual filosofía y teología, sin confundirse, se enriquecen mutuamente. El artículo finaliza con algunas consideraciones y preguntas relacionadas con las condiciones de posibilidad del diálogo entre el teólogo y el filósofo que no es creyenteABSTRACT The author seeks the foundations which provide a better understanding of the relation theology and philosophy in modern times, from the perspective of a believer. The author classifies six figures or possible ways of understanding the relationship between both disciplines: 1 the figure of identity, which claims that philosophy of a Christian is indiscernible from theology; 2 the figure of difference, according to which philosophy and theology would be non measurable disciplines; 3 the figure of influx, which emphasises the mutual conditioning of philosophy and theology from a historic--existential point of view; 4 the figure of subordination, which stands for the position that philosophy only achieves its goal with the help of theology; 5 the

A simplified model of a mechanical cooling tower with both a fill pack and a coil

Science.gov (United States)

Van Riet, Freek; Steenackers, Gunther; Verhaert, Ivan

2017-11-01

Cooling accounts for a large amount of the global primary energy consumption in buildings and industrial processes. A substantial part of this cooling demand is produced by mechanical cooling towers. Simulations benefit the sizing and integration of cooling towers in overall cooling networks. However, for these simulations fast-to-calculate and easy-to-parametrize models are required. In this paper, a new model is developed for a mechanical draught cooling tower with both a cooling coil and a fill pack. The model needs manufacturers' performance data at only three operational states (at varying air and water flow rates) to be parametrized. The model predicts the cooled, outgoing water temperature. These predictions were compared with experimental data for a wide range of operational states. The model was able to predict the temperature with a maximum absolute error of 0.59°C. The relative error of cooling capacity was mostly between ±5%.

A mascarada e a feminilidade

Directory of Open Access Journals (Sweden)

Grant Walkiria Helena

1998-01-01

Full Text Available Marcada por produções freudianas, a literatura analítica e, mais especificamente, aquela influenciada pelo ensino lacaniano, não pára de mostrar que as considerações anatômicas não são índices para falar da diferença de identidade sexual entre homens e mulheres. Diante do fato de que características masculinas continuavam presentes em mulheres adultas normais, Freud responde que ser mulher é ser mãe. A vacilação da verdade desta equação pode ser observada nas situações mais diversas nas quais podemos nos defrontar com mulheres, mães, desempenhando papéis de homens. Como pensar esta constatação? Este trabalho permitir-nos-á mostrar a imbricação do feminino e do masculino num caso de uma mulher com todas as características de uma feminilidade considerada normal, e também discutir a questão do gozo fálico e do Outro gozo - propostos por Lacan como índices de diferenciação da posição masculina e da feminina.

A farmer becomes a social pedagogue

DEFF Research Database (Denmark)

Mellon, Karsten

2016-01-01

for bachelor programmes. This article examines the case of a woman named Amy, a mature, nontraditional university college student who becomes a social pedagogue. Because of severe allergies, Amy had to quit her job as a farmer and began to study to become a social pedagogue. Becoming a social pedagogue...... is a tremendously complex process that involves taking on a new professional identity and acquiring new skills. In order to ascertain the extent of this complexity, this article uses a psychosocietal approach derived from a Danish/German life history research approach. This article offers a brief presentation...... of the theoretical and methodological framework applied before analysing the process Amy undergoes to become a social pedagogue. The analysis demonstrates that this type of significant career change is demanding and, for Amy, filled with feelings of ambivalence and defensiveness....

A Cloze Is a Cloze Is a Cloze?

Science.gov (United States)

Brown, James Dean

This study attempted to determine the effectiveness of cloze procedures as norm-referenced instruments by comparing the differential responses of four groups of college students of English as a second language on two identical cloze passages. The responses were scored using both exact-answer and acceptable-word methods. The results indicate that…

A PhD is a PhD is a PhD

OpenAIRE

Ostrow, Deborah Anne

2017-01-01

A PhD is a PhD is a PhD is a practice-based project that interrogates the process of an artist undertaking PhD research under established criteria. It consists of an exegesis, an original screenplay, and a digital film made for online viewing, with images drawn from a range of documentaries and films found on YouTube. They have been dissected, re-assembled and then re-embedded to YouTube. The source material covers topics such as medicalization of madness, the conspicuous appropriation of uni...

[As a Child of a Parent with Schizophrenia, as a Patient, and as a Psychiatrist: A Message to All JSPN Members].

Science.gov (United States)

Natsukari, Ikuko

2015-01-01

I previously published an article, entitled About "Regarding a person Who recovers". It documents the actual situation and recovery of a family member with schizophrenia, and it does not describe my recovery as a patient as a psychiatrist. At the time of publication, the main purpose was to disclose the real name of the family member. Since the disclosure, I have met many patients and families, and learned their true thoughts and strengths that I would have never known simply through consultation, and this totally changed my perceptions of them. Meanwhile, I also received many comments from medical professionals who were also family members of patients at the same time. I learned that they were struggling with conflicting emotions of being a family member as well as a professional, and I realized the isolations of families, and persistent stigma attached to psychiatric disorders. The disclosure broadened my perspectives as a psychiatrist. Now, more than 30 years after becoming a doctor, I still question myself: 'what have I done?', 'Have I listened to the voices of patients and their families?' I still have persisted, as a psychiatrist, until today. Psychiatry is a field that can be neglected if you do not question its contradictions. I think this is also why 'patient-centered recovery' has been neglected, and, as a result, psychiatry has been left behind. I often hear people asking: 'how can we increase numbers of psychiatrists?' I did not become a psychiatrist because of my own experience. I believe that, by providing medical care that the patients and their families can appreciate, from those families, some younger members will desire to become psychiatrists ; that is the way psychiatry should be developed. For that purpose, I believe it is necessary more than anything to approach each case with great care, valuing the 'real voices' of patients and their families, and respecting their strengths.

A source, a cascade, a schizoid: a heuristic proposal from the Longitudinal Study of Personality Disorders.

Science.gov (United States)

Lenzenweger, Mark F

2010-11-01

It is argued that personality pathology represents the final emergent product of a complex interaction of underlying neurobehavioral systems as well as environment inputs. A number of factors may be involved in the developmental pathway and a cascading of effects is plausible, although a unifying cascade for all personality disorders is not likely. The present study suggests a possible cascade relevant to one personality disorder: schizoid personality disorder in emerging adulthood. In brief, it is hypothesized that the absence of a relationship characterized by a rich degree of psychological proximal process in early childhood, which is associated with nurturance and the facilitation of more complex development, predicts impairment in the actualization of the affiliation system (i.e., that system that facilitates interpersonal connectedness and social bonds in human beings and is under substantial genetic influence), and this impairment in the affiliation system predicts the appearance of schizoid personality disorder symptoms in emerging adulthood (late teens/early 20s), which persists over time into emerging adulthood. The impairment in the affiliation system is argued to proceed through childhood sociality as reflected in temperament on through adult personality as reflected in communal positive emotion. Furthermore, it is also hypothesized that the relationship between proximal processes and the affiliation system maintains irrespective of other childhood temperament factors that might adversely impact early parent/caregiver and child relations. The data for a preliminary illustration of this possible cascade are drawn from The Longitudinal Study of Personality Disorders, which is a prospective, multiwave study of personality disorders, personality, and temperament in a large sample of adults drawn from a nonclinical population.

Reaction-diffusion on the fully-connected lattice: A+A\\rightarrow A

Science.gov (United States)

Turban, Loïc; Fortin, Jean-Yves

2018-04-01

Diffusion-coagulation can be simply described by a dynamic where particles perform a random walk on a lattice and coalesce with probability unity when meeting on the same site. Such processes display non-equilibrium properties with strong fluctuations in low dimensions. In this work we study this problem on the fully-connected lattice, an infinite-dimensional system in the thermodynamic limit, for which mean-field behaviour is expected. Exact expressions for the particle density distribution at a given time and survival time distribution for a given number of particles are obtained. In particular, we show that the time needed to reach a finite number of surviving particles (vanishing density in the scaling limit) displays strong fluctuations and extreme value statistics, characterized by a universal class of non-Gaussian distributions with singular behaviour.

A Benchmark Study of a Seismic Analysis Program for a Single Column of a HTGR Core

Energy Technology Data Exchange (ETDEWEB)

Kang, Ji Ho [KAERI, Daejeon (Korea, Republic of)

2016-05-15

A seismic analysis program, SAPCOR (Seismic Analysis of Prismatic HTGR Core), was developed in Korea Atomic Energy Research Institute. The program is used for the evaluation of deformed shapes and forces on the graphite blocks which using point-mass rigid bodies with Kelvin-Voigt impact models. In the previous studies, the program was verified using theoretical solutions and benchmark problems. To validate the program for more complicated problems, a free vibration analysis of a single column of a HTGR core was selected and the calculation results of the SAPCOR and a commercial FEM code, Abaqus, were compared in this study.

A numerical study of a premixed flame on a slit burner

NARCIS (Netherlands)

Somers, L.M.T.; Goey, de L.P.H.

1995-01-01

A numerical study of a premixed methane/air flame on a 4 mm slit burner is presented. A local grid refinement technique is used to deal with large gradients and curvature of all variables encountered in the flame, keeping the number of grid points within reasonable bounds. The method used here leads

Using a Science Centre as a School Lab ? a Case Story

DEFF Research Database (Denmark)

Sørensen, Helene

2004-01-01

responsibility for their own learning committed themselves to learn the scientific language. The study shows that in school science there has to be scaffolding around a project to insure that all students gain experience with science as a learning process in an environment with self-motivated, self......The study has the overall goal of finding suggestions for improving school visits to Science Centres and similar places. One such centre (Experimentarium) has established a partnership with a nearby school to investigate possibilities for cooperation. This case story tells about a project where...... tenth graders were trained to become museum ?explainers? as part of their science education. The objectives were to investigate if it was possible to obtain a quality out-of?school experience using the Experimentarium as a science lab. The intention of the study was to look at science learning...

Developing teachers, developing as a teacher: A story about a story

Directory of Open Access Journals (Sweden)

Kate Bennie

2005-10-01

Full Text Available In this paper I reflect on my changing roles as a mathematics educator, that is, as a teacher educator and as a classroom teacher in a secondary school. This is a personal account of the challenge of translating my beliefs about mathematics teaching and learning into everyday classroom practice. The presentation I use is based on the work of Rowland − the account is presented in the form of personal reflections on a story written about playing the two different roles of teacher educator and classroom teacher. I use the process of writing to try to make sense of my experiences and to explore the use of story as a research methodology. Although the story is intensely personal, there are identifiable themes that run through the narrative, which I suggest may resonate with the experience of other mathematics educators.

Silencing Bilingualism: A Day in a Life of a Bilingual Practitioner

Science.gov (United States)

Robertson, Leena H.; Drury, Rose; Cable, Carrie

2014-01-01

Based on sociocultural theories of learning, this paper draws on findings from a research project "a day in a life of a bilingual practitioner". It explores how two multilingual practitioners in English early years settings supported the learning of young 3-4 year-old children, and their parents and teachers. The paper challenges the…

Pellets - A fuel with a future

International Nuclear Information System (INIS)

2004-01-01

This special brochure presents a series of articles on the topic of wood pellets as a fuel of the future. Dr. Walter Steinmann, director of the Swiss Federal Office of Energy (SFOE) introduces the topic, stressing that the Swiss Confederation and the Cantons are supporting efforts to increase the sustainable use of wood fuels. Further articles take a closer look at pellets and their form. Pellets-fired heating units are introduced as a viable alternative to traditional oil-fired units. Tips are presented on the various ways of storing pellets. Quality-assurance aspects are examined and manufacturers and distributors of wood pellets are listed. A further article takes a closer look at a large Swiss manufacturer of pellets and describes the production process used as well as the logistics necessary for the transportation of raw materials and finished products. The brochure also presents a selection of pellet ovens and heating systems from various manufacturers. A further article illustrates the use of pellets as a means of heating apartment blocks built to the MINERGIE low-energy-consumption standard. In the example quoted, the classic combination of solar energy for the pre-heating of hot water and pellets for the central heating and hot water supply is used. The use of a buried spherical tank to store pellets - and thus the saving of space inside the building - is described in a further article that takes a look at the refurbishment of the heating system in a single-family home. Finally, various contributions presented at the Pellets Forum held in Berne in November 2003 are summarised in a short article

A mídia ensina: a criança é soberana

Directory of Open Access Journals (Sweden)

Maria Simone Vione Schwengber

2012-09-01

Full Text Available O presente artigo é parte de uma pesquisa inspirada nos campos dos Estudos de Gênero. Nele discuto a emergência de técnicas de governamento inerentes à modernidade e a criação de dispositivos educativos do imperativo da maternidade e da paternidade responsáveis. Defino esse processo educativo contemporâneo mais amplo como politização da família relacional – o casal. A partir do resultado das análises, focalizo um movimento que ensina – a criança é soberana.

A Giant or a Dwarf?

DEFF Research Database (Denmark)

Schmid, Herman

2005-01-01

EU may appear to be a giant when it can act on behalf of a united Europe, but usually it is hampered by conflicting member state interests. The EU economic and administrative resources for foreign and trade policy are quite small (on level with one of its major member states) and the hopes in many...

A deformable magnetizable worm in a magnetic field-A prototype of a mobile crawling robot

Energy Technology Data Exchange (ETDEWEB)

Zimmermann, Klaus [Faculty of Mechanical Engineering, Technische Universitaet Ilmenau, PF 10 05 65, 98684 (Germany)]. E-mail: klaus.zimmermann@tu-ilmenau.de; Naletova, Vera A. [Department of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow 119992 (Russian Federation); Institute of Mechanics, Lomonosov Moscow State University, 1, Michurinsky Pr., Moscow 119192 (Russian Federation); Zeidis, Igor [Faculty of Mechanical Engineering, Technische Universitaet Ilmenau, PF 10 05 65, 98684 (Germany); Turkov, Vladimir A. [Institute of Mechanics, Lomonosov Moscow State University, 1, Michurinsky Pr., Moscow 119192 (Russian Federation); Kolev, Emil [Faculty of Mechanical Engineering, Technische Universitaet Ilmenau, PF 10 05 65, 98684 (Germany); Lukashevich, Mikhail V. [Institute of Mechanics, Lomonosov Moscow State University, 1, Michurinsky Pr., Moscow 119192 (Russian Federation); Stepanov, Gennadij V. [State Research Institute of Chemistry and Technology of Organoelement Compounds, 38, Shosse Entuziastov, Moscow 111123 (Russian Federation)

2007-04-15

The paper deals with the deformation and worm-like motion of a magnetizable elastic body in an alternate magnetic field from an experimental and a theoretically point of view. Theoretically (analytically and numerically) calculated results of the body velocity are compared with the experimental data.

Adenosine A2A receptors and A2A receptor heteromers as key players in striatal function

Directory of Open Access Journals (Sweden)

Sergi eFerre

2011-06-01

Full Text Available A very significant density of adenosine adenosine A2A receptors (A2ARs is present in the striatum, where they are preferentially localized postsynaptically in striatopallidal medium spiny neurons (MSNs. In this localization A2ARs establish reciprocal antagonistic interactions with dopamine D2 receptors (D2Rs. In one type of interaction, A2AR and D2R are forming heteromers and, by means of an allosteric interaction, A2AR counteracts D2R-mediated inhibitory modulation of the effects of NMDA receptor stimulation in the striato-pallidal neuron. This interaction is probably mostly responsible for the locomotor depressant and activating effects of A2AR agonist and antagonists, respectively. The second type of interaction involves A2AR and D2R that do not form heteromers and takes place at the level of adenylyl-cyclase (AC. Due to a strong tonic effect of endogenous dopamine on striatal D2R, this interaction keeps A2AR from signaling through AC. However, under conditions of dopamine depletion or with blockade of D2R, A2AR-mediated AC activation is unleashed with an increased gene expression and activity of the striato-pallidal neuron and with a consequent motor depression. This interaction is probably the main mechanism responsible for the locomotor depression induced by D2R antagonists. Finally, striatal A2ARs are also localized presynaptically, in cortico-striatal glutamatergic terminals that contact the striato-nigral MSN. These presynaptic A2ARs heteromerize with A1 receptors (A1Rs and their activation facilitates glutamate release. These three different types of A2ARs can be pharmacologically dissected by their ability to bind ligands with different affinity and can therefore provide selective targets for drug development in different basal ganglia disorders.

Towards a personalized Internet: a case for a full decentralization.

Science.gov (United States)

Kermarrec, Anne-Marie

2013-03-28

The Web has become a user-centric platform where users post, share, annotate, comment and forward content be it text, videos, pictures, URLs, etc. This social dimension creates tremendous new opportunities for information exchange over the Internet, as exemplified by the surprising and exponential growth of social networks and collaborative platforms. Yet, niche content is sometimes difficult to retrieve using traditional search engines because they target the mass rather than the individual. Likewise, relieving users from useless notification is tricky in a world where there is so much information and so little of interest for each and every one of us. We argue that ultra-specific content could be retrieved and disseminated should search and notification be personalized to fit this new setting. We also argue that users' interests should be implicitly captured by the system rather than relying on explicit classifications simply because the world is by nature unstructured, dynamic and users do not want to be hampered in their actions by a tight and static framework. In this paper, we review some existing personalization approaches, most of which are centralized. We then advocate the need for fully decentralized systems because personalization raises two main issues. Firstly, personalization requires information to be stored and maintained at a user granularity which can significantly hurt the scalability of a centralized solution. Secondly, at a time when the 'big brother is watching you' attitude is prominent, users may be more and more reluctant to give away their personal data to the few large companies that can afford such personalization. We start by showing how to achieve personalization in decentralized systems and conclude with the research agenda ahead.

A masculinidade e a ideologia: a socialização masculina

Directory of Open Access Journals (Sweden)

Gabriel Ferreira de Brito

2013-12-01

Full Text Available Pretendemos, no presente artigo, refletir sobre a relação da ideologia, socialização e a masculinidade. Nosso referencial teórico para o conceito de ideologia se apoia em Marx, Mészáros e Lukács; é a partir destes pensadores que pretendemos dialogar com os estudos sobre o feminismo, a masculinidade e os gêneros em geral, pois pensamos que a influência destes três elementos pode assumir aspectos mais danosos para as mulheres e outros gêneros nas populações mais carentes da sociedade. Com referências a estatísticas sobre violência contra mulher e pesquisas qualitativas sobre sexualidade, paternidade e violência, pretendemos confirmar que o resultado de tal analise é de que a baixa instrução e a desigualdade social acentuada (principalmente no Brasil representam um perigo para os gêneros dominados. Dessa forma também será possível reafirmar que o conceito de masculinidade marginalizada pode ser observado na sociedade, permitindo uma melhor apreensão dos diferentes tipos de masculinidades possíveis na nossa cultura e em tantas outras

Towards a categorisation of behaviour determinants with a view to a ...

African Journals Online (AJOL)

Towards a categorisation of behaviour determinants with a view to a more ... personal, environmental and intervening factors on the adoption behaviour and ... most important determinants associated with behavioural change and to calculate ...

A, a Brominated Flame Retardant

Directory of Open Access Journals (Sweden)

Tomomi Takeshita

2013-01-01

Full Text Available Tetrabromobisphenol A (TBBPA, a brominated flame retardant, has been found to exacerbate pneumonia in respiratory syncytial virus- (RSV- infected mice. We examined the effect of Brazilian propolis (AF-08 on the exacerbation of RSV infection by TBBPA exposure in mice. Mice were fed a powdered diet mixed with 1% TBBPA alone, 0.02% AF-08 alone, or 1% TBBPA and 0.02% AF-08 for four weeks and then intranasally infected with RSV. TBBPA exposure increased the pulmonary virus titer and level of IFN-γ, a representative marker of pneumonia due to RSV infection, in the lungs of infected mice without toxicity. AF-08 was significantly effective in reducing the virus titers and IFN-γ level increased by TBBPA exposure. Also, AF-08 significantly reduced proinflammatory cytokine (TNF-α and IL-6 levels in the lungs of RSV-infected mice with TBBPA exposure, but Th2 cytokine (IL-4 and IL-10 levels were not evidently increased. Neither TBBPA exposure nor AF-08 treatment affected the anti-RSV antibody production in RSV-infected mice. In flow cytometry analysis, AF-08 seemed to be effective in reducing the ratio of pulmonary CD8a+ cells in RSV-infected mice with TBBPA exposure. TBBPA and AF-08 did not exhibit anti-RSV activity in vitro. Thus, AF-08 probably ameliorated pneumonia exacerbated by TBBPA exposure in RSV-infected mice by limiting excess cellular immune responses.

Trapping a single atom with a fraction of a photon using a photonic crystal nanocavity

NARCIS (Netherlands)

van Oosten, D.; Kuipers, L.

2011-01-01

We consider the interaction between a single rubidium atom and a photonic crystal nanocavity. Because of the ultrasmall mode volume of the nanocavity, an extremely strong coupling regime can be achieved in which the atom can shift the cavity resonance by many cavity linewidths. We show that this

A associação entre a periodontite e a doença renal crónica

OpenAIRE

Fernandes, Miguel Ângelo Ferreira

2017-01-01

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz A Doença periodontal (DP) tem sido cada vez mais associada a diferentes doenças sistémicas e tem-se mostrado como um potencial fator de risco para algumas delas, como as doenças cardiovasculares e a diabetes mellitus. A evidência científica sugere que a doença renal crónica (DRC) tem repercussões a nível da cavidade oral e do estado de saúde oral, nomeadamente ao poder induzir aumento do vo...

A Marshmallow and a Song

Science.gov (United States)

Kenney, Susan

2009-01-01

Music exists in time. One cannot get to the end of the song before going through the song. Is this significant for helping children wait? And can the way we present a singing game activity intensify the delay of what might be a gratifying moment at the end of the song? In this article, the author reflects on whether music can teach delayed…

Hepatic hypervitaminosis A: a familial observation.

Science.gov (United States)

Sarles, J; Scheiner, C; Sarran, M; Giraud, F

1990-01-01

Four siblings with hepatic fibrosis are described. The liver damage in these patients was secondary to chronic ingestion of massive doses of vitamin A for congenital ichthyosis. Although the extrahepatic manifestations were helpful in the diagnosis of hypervitaminosis A, the distinctive features of hepatic histopathology were confirmatory. The plasma concentrations of vitamin A and retinol-binding protein were misleading. The recovery from the liver damage in these patients was slow despite a complete withdrawal of the vitamin A intake. These cases show the importance of hepatic vitamin A assessment in the diagnosis of hepatic fibrosis.

Translocation of a polymer through a nanopore across a viscosity gradient.

Science.gov (United States)

de Haan, Hendrick W; Slater, Gary W

2013-04-01

The translocation of a polymer through a pore in a membrane separating fluids of different viscosities is studied via several computational approaches. Starting with the polymer halfway, we find that as a viscosity difference across the pore is introduced, translocation will predominately occur towards one side of the membrane. These results suggest an intrinsic pumping mechanism for translocation across cell walls which could arise whenever the fluid across the membrane is inhomogeneous. Somewhat surprisingly, the sign of the preferred direction of translocation is found to be strongly dependent on the simulation algorithm: for Langevin dynamics (LD) simulations, a bias towards the low viscosity side is found while for Brownian dynamics (BD), a bias towards the high viscosity is found. Examining the translocation dynamics in detail across a wide range of viscosity gradients and developing a simple force model to estimate the magnitude of the bias, the LD results are demonstrated to be more physically realistic. The LD results are also compared to those generated from a simple, one-dimensional random walk model of translocation to investigate the role of the internal degrees of freedom of the polymer and the entropic barrier. To conclude, the scaling of the results across different polymer lengths demonstrates the saturation of the directional preference with polymer length and the nontrivial location of the maximum in the exponent corresponding to the scaling of the translocation time with polymer length.

A.G.A. program gives utilities a leg up on benchmarking

International Nuclear Information System (INIS)

Share, J.

1997-01-01

In this era of downsizing, distribution companies are banding together under the aegis of the American Gas Association to improve their performance, ultimately saving money and jobs. The Best Practice Benchmarking program began in 1990 when New Orleans Public Service coordinated an effort by several utilities wanting to compare practices and data. It is not benchmarking in the traditional sense. Best Practices stresses functional rather than competitive or numerical benchmarking by focusing on what utilities have done to improve their operations. In a report on Best Practices, John Bayko, Director of System Operations for Consumers Gas in Toronto, noted these success stories: Building odorant storage and transport facilities were found to save one company $17,500 annually because it could buy odorant in bulk as opposed to 55-gallon drums. Upgrading its cathodic protection system helped a company realize a 40 percent reduction in corrosion leaks over a two-year period, saving $200,000 a year. Another company began studying partnering with contractors which would eliminate the need of a pipeline inspector in each crew. Those potential savings are over $2 million. This paper describes three other Best Practices related to worker safety, system mapping, and activity-based accounting. A.G.A.'s role is briefly discussed

Nanomaterials A Danger or a Promise? A Chemical and Biological Perspective

CERN Document Server

Fiévet, Fernand; Coradin, Thibaud

2013-01-01

With the increased presence of nanomaterials in commercial products such as cosmetics and sunscreens, fillers in dental fillings, water filtration process, catalysis, photovoltaic cells, bio-detection, a growing public debate is emerging on toxicological and environmental effects of direct and indirect exposure to these materials. Nanomaterials: A Danger or a Promise? forms a balanced overview of the health and environmental issues of nanoscale materials.   By considering both the benefits and risks associated with nanomaterials, Nanomaterials: A Danger or a Promise? compiles a complete and detailed image of the many aspects of the interface between nanomaterials and their real-life application. The full cycle of nanomaterials life will be presented and critically assessed to consider and answer questions such as: ·         How are nanomaterials made? ·         What they are used for? ·         What is their environmental fate? ·         Can we make them better?   Includi...

A primary sellar neuroblastoma mimicking a pituitary adenoma: A case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Gun; Heo, Young Jin; Kim, Eun Kyoung; Baek, Jin Wook; Jeong, Hae Woong; Jung, Hyun Seok [Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

2016-12-15

Intracranial neuroblastomas are uncommon malignant tumors that usually arise in the supratentorial parenchymal or paraventricular location. A primary neuroblastoma arising in the sella turcica is extremely rare. We report a case of a 76-year-old man who presented with progressive bitemporal hemianopsia. His pituitary hormone levels were within the normal range, except for slightly increased prolactin. Pituitary magnetic resonance imaging revealed a solitary sellar mass with supra- and parasellar extension that mimicked a non-functioning pituitary adenoma or meningioma. The tumor was excised by transsphenoidal resection. Histopathologic analysis revealed small cells surrounded by a dense fibrillary stroma as well as strong expression of neural markers. Hence, the patient was diagnosed with sellar neuroblastoma. Prolactin levels normalized in the immediate postoperative period, although visual disturbances persisted. Herein, we describe the clinical manifestations, MRI characteristics, and histopathologic findings of this case.

Teoría de Juegos Aplicada a la Economía

OpenAIRE

Hernández Rodríguez, Adrián

2017-01-01

La Teoría de Juegos es una rama de las matemáticas y la economía que se encarga de analizar unas situaciones denominadas juegos, en las que dos o más jugadores deben decidir qué decisión tomar en función de las decisiones que puedan tomar los otros. Esta rama comenzó a tomar una gran importancia en la década de 1990, con la consecución en 1994 del Premio Nobel de Economía por parte de John Forbes Nash, John Harsanyi y Reinhard Selten. La Teoría de Juegos puede utilizarse para resolver situ...

A FOTOGRAFIA ENTRE A ARTE POPULAR E A ARTE ERUDITA

Directory of Open Access Journals (Sweden)

Marcos Fabris

2013-09-01

Full Text Available Este artigo pretende discutir alguns dos aspectos que marcam o estabelecimento e a dissolução das fronteiras entre dois pólos convencionalmente descritos como arte culta e arte popular, tecendo paralelos entre o teatro de variedades, forma de expressão popular por excelência, e a fotografia, expressão artística que desde seus primórdios circula entre os dois extremos deste contínuo. Nestes termos, ambiciona-se verificar como determinadas condições sócio-históricas favorecem a criação de recursos formais que minimizam, ou suprimem, tais distinções consagradas pela crítica de arte.

A unilateral optic perineuritis in a teenager - A case report.

Science.gov (United States)

Ameilia, Ahmad; Shatriah, Ismail; Wan-Hitam, Wan Hazabbah; Yunus, Rohaizan

2015-06-01

Optic perineuritis is an uncommon inflammatory disorder that involves optic nerve sheath. Numerous case reports have been published on optic perineuritis in adults, the majority of whom had bilateral presentation. There are limited data on optic perineuritis occurring in pediatric patients. We report a teenager who presented with a unilateral sign that mimicked the presentation of optic neuritis. The orbit and brain magnetic resonance imaging confirmed features of unilateral optic perineuritis. She was treated with a high dose of corticosteroids for 2weeks, and her final visual outcome was satisfactory. No signs of relapse were noted during follow-up visits. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Is the A1 a resonance

International Nuclear Information System (INIS)

Morgan, D.

1975-06-01

Data on diffractive and charge exchange 3π production in the Jsup(P) = 1 + state are shown to favour a resonance interpretation, although with a somewhat higher mass than the conventional A 1 bump. Data are fitted using a two-component model for the production amplitude. The first component comprises the Deck (Born) contribution and its re-scattering corrections; the second represents the so-called 'direct-production' term. The conventional isobar approximation to unitarity is demanded; this forbids the intrusion of additional phases in the Born term, such as arise from projecting a Reggeized Deck amplitude. As a consequence, the phase of the 1 + S 3π production amplitude is predicted to execute a standard resonant variation with Msup(3π). This carries a striking implication for the interfering 'background' waves, 1 + P, 2 - P, 0 - S, relative to which the 1 + S amplitude fails to register any appreciable phase variation in phenomenological analyses. There is no obvious objection to ascribing resonance status to these three channels, of which only one, the 0 - , demands a new (π ') resonance. A running theme, which recurs whenever the results of phenomenological 3-body phase shift analyses are appealed to, is that dynamical features are best viewed in terms of effective matrix elements rather than partial cross-sections. (author)

Proposal for a Similar Question Search System on a Q&A Site

Directory of Open Access Journals (Sweden)

Katsutoshi Kanamori

2014-06-01

Full Text Available There is a service to help Internet users obtain answers to specific questions when they visit a Q&A site. A Q&A site is very useful for the Internet user, but posted questions are often not answered immediately. This delay in answering occurs because in most cases another site user is answering the question manually. In this study, we propose a system that can present a question that is similar to a question posted by a user. An advantage of this system is that a user can refer to an answer to a similar question. This research measures the similarity of a candidate question based on word and dependency parsing. In an experiment, we examined the effectiveness of the proposed system for questions actually posted on the Q&A site. The result indicates that the system can show the questioner the answer to a similar question. However, the system still has a number of aspects that should be improved.

A model of a social chatbot

NARCIS (Netherlands)

Augello, Agnese; Gentile, Manuel; Weideveld, Lucas; Dignum, Frank

2016-01-01

Traditional chatbots lack the capability to correctly manage conversations according to the social context. However a dialogue is a joint activity that must consider both individual and social processes. In this work we propose a model of a social chatbot able to choose the most suitable dialogue

[A toddler with a mandibular fracture].

Science.gov (United States)

van der Linden, E L; Bun, R J; van Os, E

2017-01-01

Mandibular fractures are rare in children. Symptoms of these fractures include preauricular pain and swelling, trismus and pain when opening the mouth, and they are often preceded by a fall on the chin. If the diagnosis is missed they may have serious consequences for the growth and development of the jaw. A 3-year-old boy was referred with a swelling in his left cheek, fever and vomiting. Two days earlier he had fallen on his chin. At physical examination he had severe preauricular pain on palpation and a trismus. The patient was admitted because of suspicion of a viral parotitis and the threat of dehydration. After discharge, he went to the dentist for examination of a molar that was painful to the touch. The dentist performed an orthopantomogram and discovered a fracture of the left mandibular collum. Any child with trauma to the chin should be observed for symptoms of a mandibular fracture, and if it seems necessary non-invasive radiographic examination should be performed.

A face in a (temporal) crowd.

Science.gov (United States)

Hacker, Catrina M; Meschke, Emily X; Biederman, Irving

2018-03-20

Familiar objects, specified by name, can be identified with high accuracy when embedded in a rapidly presented sequence of images at rates exceeding 10 images/s. Not only can target objects be detected at such brief presentation rates, they can also be detected under high uncertainty, where their classification is defined negatively, e.g., "Not a Tool." The identification of a familiar speaker's voice declines precipitously when uncertainty is increased from one to a mere handful of possible speakers. Is the limitation imposed by uncertainty, i.e., the number of possible individuals, a general characteristic of processes for person individuation such that the identifiability of a familiar face would undergo a similar decline with uncertainty? Specifically, could the presence of an unnamed celebrity, thus any celebrity, be detected when presented in a rapid sequence of unfamiliar faces? If so, could the celebrity be identified? Despite the markedly greater physical similarity of faces compared to objects that are, say, not tools, the presence of a celebrity could be detected with moderately high accuracy (∼75%) at rates exceeding 7 faces/s. False alarms were exceedingly rare as almost all the errors were misses. Detection accuracy by moderate congenital prosopagnosics was lower than controls, but still well above chance. Given the detection of the presence of a celebrity, all subjects were almost always able to identify that celebrity, providing no role for a covert familiarity signal outside of awareness. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lipoprotein(a) and ischemic heart disease-A causal association? A review

DEFF Research Database (Denmark)

Kamstrup, P.R.

2010-01-01

association of LPA copy number variants, influencing levels of lipoprotein(a), with risk of IHD. In conclusion, results from epidemiologic, in vitro, animal, and genetic epidemiologic studies support a causal association of lipoprotein(a) with risk of IHD, while results from randomized clinical trials...

A Fifa, a democracia e a soberania: tensões e paradoxos

Directory of Open Access Journals (Sweden)

Maria Fernanda Salcedo Repoles

2015-06-01

Full Text Available http://dx.doi.org/10.5007/2177-7055.2015v36n70p211 O artigo parte das declarações de dirigentes da FIFA no contexto das manifestações de junho de 2013, segundo as quais a democracia representaria obstáculo para a realização da Copa do Mundo. Busca-se analisar ainda o suposto “território FIFA” na Lei Geral da Copa.  O objetivo é refletir sobre esses dois aspectos a partir das tensões geradas na modernidade entre a realização das promessas de soberania e de democracia e as pressões advindas das forças de mercado notadamente volúveis e imprevisíveis. As manifestações políticas podem ser entendidas como reação à privatização da esfera pública e a lembrança de que a fixação de “territórios” pode também ser oportunidade de encontro e de exercício do dissenso.

A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A

Science.gov (United States)

Keefe, A. D.; Newton, G. L.; Miller, S. L.

1995-01-01

The involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics--a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world could have preceded the RNA world. The components of coenzyme A have been shown to be probable prebiotic compounds: beta-alanine, pantoyl lactone and cysteamine and possibly adenosine. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, beta-alanine and cysteamine at temperatures as low as 40 degrees C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 degrees C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.

A QUESTION OF STRATEGY:TO BE A PIONEER OR A FOLLOWER?

OpenAIRE

Đorđe Kaličanin

2008-01-01

One of the most important questions faced by business leaders in the strategic management process is a choice of timing to launch new product/technologies and enter new markets. There are two options: to be a pioneer or to be a follower. Both have advantages and risks. Pioneers often have higher profitability, greater market share, and a longer business life, but the relative success of each strategy depends on several factors, both internal and external (pace of evolution of technology and m...

Homenagem a Ecléa Bosi

Directory of Open Access Journals (Sweden)

Marilena Chauí

2008-03-01

Full Text Available Neste ensaio, buscamos a principal contribuição de Ecléa Bosi para a Psicologia Social, qual seja, a relação entre teoria, método e técnicas de pesquisa e militância social, política e cultural, a partir da definição da psicologia como fenomenologia dos atos expressivos e da relação de amizade entre o pesquisador e o pesquisado como pessoa.