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Sample records for cilengitide enhances efficacy

  1. The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus

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    Fujii, Kentaro; Kurozumi, Kazuhiko; Ichikawa, Tomotsugu; Onishi, Manabu; Shimazu, Yosuke; Ishida, Joji; Chiocca, E. Antonio; Kaur, Balveen; Date, Isao

    2016-01-01

    Oncolytic viral (OV) therapy has been considered as a promising treatment modality for brain tumors. Vasculostatin, the fragment of brain-specific angiogenesis inhibitor-1, shows anti-angiogenic activity against malignant gliomas. Previously, a vasculostatin-expressing oncolytic HSV-1, Rapid Antiangiogenesis Mediated By Oncolytic virus (RAMBO), was reported to have a potent antitumor effect. Here, we investigated the therapeutic efficacy of RAMBO and cilengitide, an integrin inhibitor, combination therapy for malignant glioma. In vitro, tube formation was significantly decreased in RAMBO and cilengitide combination treatment compared to RAMBO or cilengitide monotherapy. Moreover, combination treatment induced a synergistic suppressive effect on endothelial cell migration compared to the control virus. RAMBO, combined with cilengitide, induced synergistic cytotoxicity on glioma cells. In the caspase-8 and -9 assays, the relative absorption of U87ΔEGFR cell clusters treated with cilengitide and with RAMBO was significantly higher than of those treated with control. In addition, the activity of caspase 3/7 was significantly increased with combination therapy. In vivo, there was a significant increase in the survival of mice treated with combination therapy compared to RAMBO or cilengitide monotherapy. These results indicate that cilengitide enhanced vasculostatin-expressing OV therapy for malignant glioma and provide a rationale for designing future clinical trials combining these two agents. PMID:23827879

  2. In vitro study of combined cilengitide and radiation treatment in breast cancer cell lines

    International Nuclear Information System (INIS)

    Brain metastasis from breast cancer poses a major clinical challenge. Integrins play a role in regulating adhesion, growth, motility, and survival, and have been shown to be critical for metastatic growth in the brain in preclinical models. Cilengitide, an αvβ3/αvβ5 integrin inhibitor, has previously been studied as an anti-cancer drug in various tumor types. Previous studies have shown additive effects of cilengitide and radiation in lung cancer and glioblastoma cell lines. The ability of cilengitide to enhance the effects of radiation was examined preclinically in the setting of breast cancer to assess its possible efficacy in the setting of brain metastasis from breast cancer. Our panel of breast cells was composed of four cell lines: T-47D (ER/PR+, Her2-, luminal A), MCF-7 (ER/PR+, Her2-, luminal A), MDA-MB-231 (TNBC, basal B), MDA-MB-468 (TNBC, basal A). The presence of cilengitide targets, β3 and β5 integrin, was first determined. Cell detachment was determined by cell counting, cell proliferation was determined by MTS proliferation assay, and apoptosis was measured by Annexin V staining and flow cytometry. The efficacy of cilengitide treatment alone was analyzed, followed by assessment of combined cilengitide and radiation treatment. Integrin β3 knockdown was performed, followed by cilengitide and radiation treatment to test for incomplete target inhibition by cilengitide, in high β3 expressing cells. We observed that all cell lines examined expressed both β3 and β5 integrin and that cilengitide was able to induce cell detachment and reduced proliferation in our panel. Annexin V assays revealed that a portion of these effects was due to cilengitide-induced apoptosis. Combined treatment with cilengitide and radiation served to further reduce proliferation compared to either treatment alone. Following β3 integrin knockdown, radiosensitization in combination with cilengitide was observed in a previously non-responsive cell line (MDA-MB-231

  3. Cilengitide inhibits metastatic bone colonization in a nude rat model.

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    Bretschi, Maren; Merz, Maximilian; Komljenovic, Dorde; Berger, Martin R; Semmler, Wolfhard; Bäuerle, Tobias

    2011-10-01

    Integrins αvβ3 and αvβ5 are considered to play an important role in the pathogenesis of breast cancer bone metastases. This study investigates the effects of the αvβ3/αvβ5 integrin-specific inhibitor cilengitide during early metastatic bone colonization. The impact of cilengitide on the migration, invasion and proliferation of MDA-MB-231 human breast carcinoma cells as well as on bone resorption by osteoclasts was investigated in vitro. For in vivo experiments, nude rats were treated with cilengitide for 30 days starting one day after site-specific tumor cell inoculation in the hind leg, and the course of metastatic changes in bone was followed using flat-panel volumetric computed tomography (VCT) and magnetic resonance imaging (MRI). Vascular changes in bone metastases were investigated using dynamic contrast-enhanced (DCE-) MRI-derived parameters amplitude A and exchange rate coefficient kep. In vitro, cilengitide treatment resulted in a decrease in proliferation, migration and invasion of MDA-MB-231 cells, as well as of osteoclast activity. In vivo, the development of bone metastasis in the hind leg of rats was not prevented by adjuvant cilengitide treatment, but cilengitide reduced the volumes of osteolytic lesions and respective soft tissue tumors of developing bone metastases as assessed with VCT and MRI, respectively. DCE-MRI revealed significant changes in the A and kep parameters including decreased relative blood volume and increased vessel permeability after cilengitide treatment indicating vessel remodeling. In conclusion, during early pathogenic processes of bone colonization, cilengitide treatment exerted effects on tumor cells, osteoclasts and vasculature reducing the skeletal lesion size of experimental skeletal metastases. PMID:21725616

  4. Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery.

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    Gilbert, Mark R; Kuhn, John; Lamborn, Kathleen R; Lieberman, Frank; Wen, Patrick Y; Mehta, Minesh; Cloughesy, Timothy; Lassman, Andrew B; Deangelis, Lisa M; Chang, Susan; Prados, Michael

    2012-01-01

    Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the αvβ3 and αvβ5 integrins. Preclinical studies demonstrate antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy and tumor delivery of cilengitide in patients with recurrent glioblastoma. Patients with recurrent glioblastoma who require a surgical resection for optimal clinical care received 3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1) prior to undergoing tumor resection with corresponding blood samples for plasma to tumor comparisons. After recovery from surgery, patients were treated with cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). The study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for efficacy. The 6-month progression free survival rate was 12%. Cilengitide was detected in all tumor specimens with higher levels in the group receiving 2000 mg dosing while corresponding plasma concentrations were low, often below the lower limit of detection. These results confirm drug delivery and possibly retention in tumor. This study provides evidence that with established dosing, cilengitide is adequately delivered to the tumor, although as a single agent, efficacy in recurrent glioblastoma is modest. However, these results demonstrating drug delivery to tumor do support continued investigation of this agent as preliminary results from recent studies combining cilengitide with cytotoxic therapies are promising. PMID:21739168

  5. Cilengitide inhibits progression of experimental breast cancer bone metastases as imaged noninvasively using VCT, MRI and DCE-MRI in a longitudinal in vivo study.

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    Bäuerle, Tobias; Komljenovic, Dorde; Merz, Maximilian; Berger, Martin R; Goodman, Simon L; Semmler, Wolfhard

    2011-05-15

    The aim of this study was to investigate the effect of inhibiting αvβ(3)/α(v) β(5) integrins by cilengitide in experimentally induced breast cancer bone metastases using noninvasive imaging techniques. For this purpose, nude rats bearing established breast cancer bone metastases were treated with cilengitide, a small molecule inhibitor of αvβ(3) and αvβ(5) integrins (75 mg/kg, five days per week; n = 12 rats) and compared to vehicle-treated control rats (n = 12). In a longitudinal study, conventional magnetic resonance imaging (MRI) and flat panel volumetric computed tomography were used to assess the volume of the soft tissue tumor and osteolysis, respectively, and dynamic contrast-enhanced (DCE-) MRI was performed to determine functional parameters of the tumor vasculature reflecting blood volume and blood vessel permeability. In rats treated with cilengitide, VCT and MRI showed that osteolytic lesions and the respective bone metastatic soft tissue tumors progressed more slowly than in vehicle-treated controls. DCE-MRI indicated a decrease in blood volume and an increase in vessel permeability and immunohistology revealed increased numbers of immature vessels in cilengitide-treated rats compared to vehicle controls. In conclusion, treatment of experimental breast cancer bone metastases with cilengitide resulted in pronounced antiresorptive and antitumor effects, suggesting that αvβ(3)/αvβ(5) inhibition may be a promising therapeutic approach for bone metastases. PMID:20648558

  6. Cilengitide with metronomic temozolomide, procarbazine, and standard radiotherapy in patients with glioblastoma and unmethylated MGMT gene promoter in ExCentric, an open-label phase II trial.

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    Khasraw, Mustafa; Lee, Adrian; McCowatt, Sally; Kerestes, Zoltan; Buyse, Marc E; Back, Michael; Kichenadasse, Ganessan; Ackland, Stephen; Wheeler, Helen

    2016-05-01

    Newly diagnosed glioblastoma multiforme with unmethylated MGMT promoter has a poor prognosis, with a median survival of 12 months. This phase II study investigated the efficacy and safety of combining the selective integrin inhibitor cilengitide with a combination of metronomic temozolomide and procarbazine for these patients. Eligible patients (newly diagnosed, histologically confirmed supratentorial glioblastoma with unmethylated MGMT promoter) were entered into this multicentre study. Cilengitide (2000 mg IV twice weekly) was commenced 1 week prior to radiotherapy combined with daily temozolomide (60 mg/m(2)) and procarbazine (50 or 100 mg) and, after 4 weeks' break, followed by six adjuvant cycles of temozolomide (50-60 mg/m(2)) and procarbazine (50 or 100 mg) on days 1-20, every 28 days. Cilengitide was continued for up to 12 months or until disease progression or unacceptable toxicity. The primary endpoint for efficacy was a 12-month overall survival rate of 65 %. Twenty-nine patients completed study treatment. Sixteen patients survived for 12 months or more, an overall survival rate of 55 %. The median overall survival was 14.5 months (95 % CI 11.1-19.6) and the median progression-free survival was 7.4 months (95 % CI 6.1-8). Cilengitide combined with metronomic temozolomide and procarbazine in MGMT-promoter unmethylated glioblastoma did not improve survival compared with historical data and does not warrant further investigation. PMID:26935578

  7. Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome

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    Weller, Michael; Nabors, Louis Burt; Gorlia, Thierry; Leske, Henning; Rushing, Elisabeth; Bady, Pierre; Hicking, Christine; Perry, James; Hong, Yong-Kil; Roth, Patrick; Wick, Wolfgang; Goodman, Simon L.; Hegi, Monika E.; Picard, Martin; Moch, Holger; Straub, Josef; Stupp, Roger

    2016-01-01

    Integrins αvβ3 and αvβ5 regulate angiogenesis and invasiveness in cancer, potentially by modulating activation of the transforming growth factor (TGF)-β pathway. The randomized phase III CENTRIC and phase II CORE trials explored the integrin inhibitor cilengitide in patients with newly diagnosed glioblastoma with versus without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. These trials failed to meet their primary endpoints. Immunohistochemistry was used to assess the levels of the target integrins of cilengitide, αvβ3 and αvβ5 integrins, of αvβ8 and of their putative target, phosphorylation of SMAD2, in tumor tissues from CENTRIC (n=274) and CORE (n=224). αvβ3 and αvβ5 expression correlated well in tumor and endothelial cells, but showed little association with αvβ8 or pSMAD2 levels. In CENTRIC, there was no interaction between the biomarkers and treatment for prediction of outcome. In CORE, higher αvβ3 levels in tumor cells were associated with improved progression-free survival by central review and with improved overall survival in patients treated with cilengitide. Integrins αvβ3, αvβ5 and αvβ8 are differentially expressed in glioblastoma. Integrin levels do not correlate with the activation level of the canonical TGF-β pathway. αvβ3 integrin expression may predict benefit from integrin inhibition in patients with glioblastoma lacking MGMT promoter methylation. PMID:26918452

  8. Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro.

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    Maurer, Gabriele D; Tritschler, Isabel; Adams, Barbara; Tabatabai, Ghazaleh; Wick, Wolfgang; Stupp, Roger; Weller, Michael

    2009-12-01

    Cilengitide is a cyclic peptide antagonist of integrins alphavbeta3 and alphavbeta5 that is currently being evaluated as a novel therapeutic agent for recurrent and newly diagnosed glioblastoma. Its mode of action is thought to be mainly antiangiogenic but may include direct effects on tumor cells, notably on attachment, migration, invasion, and viability. In this study we found that, at clinically relevant concentrations, cilengitide (1-100 microM) induces detachment in some but not all glioma cell lines, while the effect on cell viability is modest. Detachment induced by cilengitide could not be predicted by the level of expression of the cilengitide target molecules, alphavbeta3 and alphavbeta5, at the cell surface. Glioma cell death induced by cilengitide was associated with the generation of caspase activity, but caspase activity was not required for cell death since ectopic expression of cytokine response modifier (crm)-A or coexposure to the broad-spectrum caspase inhibitor zVAD-fmk was not protective. Moreover, forced expression of the antiapoptotic protein marker Bcl-X(L) or altering the p53 status did not modulate cilengitide-induced cell death. No consistent effects of cilengitide on glioma cell migration or invasiveness were observed in vitro. Preliminary clinical results indicate a preferential benefit from cilengitide added to temozolomide-based radiochemotherapy in patients with O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation. Accordingly, we also examined whether the MGMT status determines glioma cell responses to cilengitide alone or in combination with temozolomide. Neither ectopic expression of MGMT in MGMT-negative cells nor silencing the MGMT gene in MGMT-positive cells altered glioma cell responses to cilengitide alone or to cilengitide in combination with temozolomide. These data suggest that the beneficial clinical effects derived from cilengitide in vivo may arise from altered perfusion, which promotes temozolomide

  9. Cilengitide inhibits proliferation and differentiation of human endothelial progenitor cells in vitro

    International Nuclear Information System (INIS)

    Bone marrow derived hematopoietic stem cells can function as endothelial progenitor cells. They are recruited to malignant tumors and differentiate into endothelial cells. This mechanism of neovascularization termed vasculogenesis is distinct from proliferation of pre-existing vessels. To better understand vasculogenesis we developed a cell culture model with expansion and subsequent endothelial differentiation of human CD133+ progenitor cells in vitro. αvβ3-integrins are expressed by endothelial cells and play a role in the attachment of endothelial cells to the extracellular matrix. We investigated the effect of Cilengitide, a peptide-like, high affinity inhibitor of αvβ3- and αvβ5-integrins in our in vitro system. We could show expression of αvβ3-integrin on 60 ± 9% of non-adherent endothelial progenitors and on 91 ± 7% of differentiated endothelial cells. αvβ3-integrin was absent on CD133+ hematopoietic stem cells. Cilengitide inhibited proliferation of CD133+ cells in a dose-dependent manner. The development of adherent endothelial cells from expanded CD133+ cells was reduced even stronger by Cilengitide underlining its effect on integrin mediated cell adhesion. Expression of endothelial antigens CD144 and von Willebrand factor on differentiating endothelial precursors was decreased by Cilengitide. In summary, Cilengitide inhibits proliferation and differentiation of human endothelial precursor cells underlining its anti-angiogenic effects

  10. A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974 and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer

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    Katz Frieder

    2006-12-01

    Full Text Available Abstract Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. Methods A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS, response rate, quality of life (QoL, effects on biological markers of disease (CA 19.9 and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor, and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. Results Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. Conclusion There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies

  11. A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with

  12. The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines

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    Heiduschka, G. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Medical University of Vienna, Clinical Pharmacology, Vienna (Austria); Lill, C.; Schneider, S.; Kotowski, U.; Thurnher, D. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Comprehensive Cancer Center, Vienna (Austria); Seemann, R. [Medical University of Vienna, Craniomaxillofacial and Oral Surgery, Vienna (Austria); Kornek, G. [Medical University of Vienna, Internal Medicine, Vienna (Austria); Schmid, R. [Medical University of Vienna, Radiotherapy and Radiobiology, Vienna (Austria)

    2014-05-15

    Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity. (orig.) [German] Durch ihre Rolle bei der Angiogenese sind Integrine ein attraktives Ziel in der onkologischen Forschung. Der derzeit vielversprechendste Inhibitor dieser Molekuele ist Cilengitide, welches bereits in klinischen Studien getestet wird. Dennoch ist erst wenig ueber die zellulaeren Vorgaenge bekannt, welche durch Cilengitide in Kopf-Hals-Karzinomen (HNSCC) insbesondere in Kombination mit Strahlentherapie und

  13. In vitro and in vivo drug disposition of cilengitide in animals and human

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    Dolgos, Hugues; Freisleben, Achim; Wimmer, Elmar; Scheible, Holger; Krätzer, Friedrich; Yamagata, Tetsuo; Gallemann, Dieter; Fluck, Markus

    2016-01-01

    Abstract Cilengitide is very low permeable (1.0 nm/sec) stable cyclic pentapeptide containing an Arg‐Gly‐Asp motif responsible for selective binding to αvβ3 and αvβ5 integrins administered intravenously (i.v.). In vivo studies in the mouse and Cynomolgus monkeys showed the major component in plasma was unchanged drug (>85%). These results, together with the absence of metabolism in vitro and in animals, indicate minimal metabolism in both species. The excretion of [14C]‐cilengitide showed pro...

  14. Enhancing the antibacterial efficacy of isoeugenol by emulsion encapsulation.

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    Krogsgård Nielsen, Christina; Kjems, Jørgen; Mygind, Tina; Snabe, Torben; Schwarz, Karin; Serfert, Yvonne; Meyer, Rikke Louise

    2016-07-16

    Food spoilage and foodborne illnesses are two global challenges for food manufacturers. Essential oils are natural antibacterials that could have a potential for use in food preservation. Unfortunately high concentrations are needed to obtain the desired antibacterial effect, and this limits their use in food due to their adverse organoleptic properties. Encapsulation could make essential oils more effective by concentrating them in the aqueous phase of the food matrix where the bacteria are present. Here we tested encapsulation of the essential oil isoeugenol in spray-dried emulsions as a means of making isoeugenol a more effective antibacterial for use in food preservation. We used β-lactoglobulin and n-OSA starch as emulsifiers, and some emulsions were coated with positively charged chitosan to promote the contact with bacteria through electrostatic interactions. The antibacterial efficacy was quantified as the minimal bactericidal concentration in growth media, milk and carrot juice. The emulsion encapsulation system developed in this study provided high loading capacities, and encapsulation enhanced the efficacy of isoeugenol against Gram-positive and -negative bacteria in media and carrot juice but not in milk. Chitosan-coating did not enhance the efficacy further, possibly due to the aggregation of the chitosan-coated emulsions. The encapsulation system is easy to upscale and should be applicable for encapsulation of similar essential oils. Therefore, we believe it has potential to be used for natural food preservation. PMID:27089032

  15. Enhancement of optical skin clearing efficacy using a microneedle roller

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    Yoon, Jinhee; Son, Taeyoon; Choi, Eung-ho; Choi, Bernard; Nelson, J. Stuart; Jung, Byungjo

    2009-01-01

    Light scattering in biological tissues can be reduced by using optical clearing agents. Various physical methods in conjunction with agents have been studied to enhance the optical clearing efficacy of skin for diagnostic and therapeutic applications. In this study, we propose a new physical method to enhance the optical clearing potential of topically applied glycerol. A microneedle roller is used to easily create numerous transdermal microchannels prior to glycerol application. The optical clearing efficacy of skin is quantitatively evaluated with the use of a modulation transfer function target placed underneath ex vivo porcine skin samples. From cross-polarized images acquired at various time points after glycerol application, we find that samples treated with the microneedle roller resulted in an approximately two-fold increase in contrast compared to control samples 30 min after glycerol application. In conclusion, our data suggest that the microneedle roller can be a good physical method to enhance transdermal delivery of optical clearing agents, and hence their optical clearing potential over large regions of skin. PMID:18465952

  16. Leadership and Leader Developmental Self-Efficacy: Their Role in Enhancing Leader Development Efforts.

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    Murphy, Susan Elaine; Johnson, Stefanie K

    2016-03-01

    This chapter describes the role of two types of self-efficacy-leader self-efficacy and leader developmental efficacy-for enhancing leadership development. Practical implications for designing and developing leadership programs that take into account these two types of self-efficacy are discussed. PMID:26895265

  17. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

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    Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm3 increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors

  18. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

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    Choi, Seo-Hyun; Nam, Jae-Kyung; Jang, Junho; Lee, Hae-June, E-mail: hjlee@kcch.re.kr; Lee, Yoon-Jin, E-mail: yjlee8@kcch.re.kr

    2015-06-26

    Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.

  19. How to enhance the efficacy of health network growth.

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    Weil, T P

    2000-01-01

    In almost every American metropolitan area, health executives are busily enhancing the efficacy of their health networks by corporately restructuring so that their organization can become a fiscally and politically powerful oligopoly or a regulated monopoly. When the formation of these alliances are initially announced by the local media, they are reported to be vehicles to enhance access, social equity and quality of care, and to reduce costs. Since an increasing number of these health networks are currently experiencing fiscal, cultural and other difficulties, it is critical to study: (a) what factors should be considered when developing an effective and efficient health network?; (b) what are the practical issues in their strategic formation and management so they eventually achieve their full potential?; and (c) why will some divestitures among these health networks occur and how will these corporate 'spin offs' impact on consumers, providers, insurers and governmental agencies? Within the next decade the United States will face some inevitable economic difficulties. At that time, enhancing access and reducing costs will become more critical issues for health networks. These alliances may then need to become more responsive to consumer pressures as the Americans shift their political proclivities from the current quasi-competitive to a more quasi-regulatory position. In this context, the use of global budgetary targets is discussed as a possible option in the United States to constrain costs, an approach used in almost all other western industrialized nations. PMID:10947565

  20. Evaluation of treatment response of cilengitide in an experimental model of breast cancer bone metastasis using dynamic PET with 18F-FDG.

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    Cheng, Caixa; Komljenovic, Dorde; Pan, Leyun; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig; Bäuerle, Tobias

    2011-01-01

    The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases. Rats were inoculated with MDA-MB-231 breast cancer cells, followed by the development of lytic lesions in the hind leg. Rats with lytic lesions were treated with cilengitide five times weekly on a continuous basis from days 30 to 55 after tumor cell inoculation. Dynamic PET studies with (18)F-FDG were performed in untreated (n=9), controlled (n=4) and treated rats (n=6). The data were assessed using learning-machine two-tissue compartmental analysis. The (18)F-FDG kinetic parameters obtained by two-tissue compartmental model learning-machine showed significant differences when individual parameters were compared between the control group and treated animals. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data provided us with evidence to identify those tumors that demonstrated effect of cilengitide treatment. The transport rate K1 and the phosphorylation rate k3 were significantly different (P=0.033 and 0.038, respectively). Classification analysis based on support vector machines ranking feature elimination of the combination of PET parameters revealed an overall accuracy of 80.0% between treated animals and the control group. We were able to identify 83.3% treated animals compared with the control group based on k2 and VB. In conclusion, the results revealed that cilengitide treatment of experimental breast cancer bone metastases had a significant therapeutic impact on (18)F-FDG kinetics. PMID:21512659

  1. Validation of an instrument for mathematics enhancement teaching efficacy of Pacific Northwest agricultural educators

    Science.gov (United States)

    Jansen, Daniel J.

    Teacher efficacy continues to be an important area of study in educational research. This study tested an instrument designed to assess the perceived efficacy of agricultural education teachers when engaged in lessons involving mathematics instruction. The study population of Oregon and Washington agricultural educators utilized in the validation of the instrument revealed important demographic findings and specific results related to teacher efficacy for the study population. An instrument was developed from the assimilation of three scales previously used and validated in efficacy research. Participants' mathematics teaching efficacy was assessed using a portion of the Mathematics Teaching Efficacy Beliefs Instrument (MTEBI), and personal mathematics efficacy was evaluated by the mathematics self-belief instrument which was derived from the Betz and Hackett's Mathematics Self-Efficacy Scale. The final scale, the Teachers' Sense of Efficacy Scale (TSES) created by Tschannen-Moran and Woolfolk Hoy, examined perceived personal teaching efficacy. Structural equation modeling was used as the statistical analyses tool to validate the instrument and examine correlations between efficacy constructs used to determine potential professional development needs of the survey population. As part of the data required for validation of the Mathematics Enhancement Teaching Efficacy instrument, demographic information defining the population of Oregon and Washington agricultural educators was obtained and reported. A hypothetical model derived from teacher efficacy literature was found to be an acceptable model to verify construct validity and determine strength of correlations between the scales that defined the instrument. The instrument produced an alpha coefficient of .905 for reliability. Both exploratory and confirmatory factor analyses were used to verify construct and discriminate validity. Specifics results related to the survey population of agricultural educators

  2. STUDENT TEACHING ENHANCEMENT PROGRAM (STEP) AND PRESERVICE TEACHERS’ TEACHING EFFICACY IN SCIENCE

    OpenAIRE

    MONTEBON, Darryl Roy

    2015-01-01

    The present paper discusses the effect of the Student Teaching Enhancement Program (STEP) provided to science preservice teachers in a teacher education institute on their teaching efficacy. The STEP is a program that is designed to impact the areas that influence preservice teachers’ teaching efficacy. Teaching efficacy is an important construct that should be enriched among teachers since the teachers’ belief on their ability to teach significantly affects their performance in the classroom...

  3. Student Teaching Enhancement Program (STEP) and Preservice Teachers’ Teaching Efficacy in Science

    OpenAIRE

    Darryl Roy T. Montebon

    2015-01-01

    The present paper discusses the effect of the Student Teaching Enhancement Program (STEP) provided to science preservice teachers in a teacher education institute on their teaching efficacy. The STEP is a program that is designed to impact the areas that influence preservice teachers’ teaching efficacy. Teaching efficacy is an important construct that should be enriched among teachers since the teachers’ belief on their ability to teach significantly affects their performance in the classroom...

  4. Enhancement of Luminous Efficacy by Random Patterning of Phosphor Matrix

    Science.gov (United States)

    Fellows, Natalie; Masul, Hisashi; Diana, Frederic; Denbaars, Steven P.; Nakamura, Shuji

    We have demonstrated the ability to increase the luminous flux and luminous efficacy of white light-emitting diodes (LEDs) by randomly patterning the surface of the yellow phosphor matrix. The phosphor was moved away from the LED die by placing it on top of a silicone optic and then roughening the surface of the phosphor/resin mixture. It was found that the roughening increases the luminous flux and efficacy by 10% over the smooth, non-patterned phosphor mixture. The roughened sample’s operating voltage, luminous flux, luminous efficacy, CCT, color coordinates, and CRI were 3.2 V, 7.4 lm, 115.6 lm/W, 4244 K, (0.388, 0.448), and 61 at 20 mA, CW, and room temperature operation. A brief presentation on phosphor scattering is introduced to help explain the effect of the roughening.

  5. Enhancing Entrepreneurial Self-Efficacy through Vocational Entrepreneurship Education Programmes

    Science.gov (United States)

    Maritz, Alex; Brown, Chris

    2013-01-01

    The purpose of this study is to report the results of a longitudinal evaluation of a vocational entrepreneurship education programme (EEP) using entrepreneurial self-efficacy (ESE) measures. An empirical, mixed methods longitudinal and effectuation scale was used to measure ESE scores. Results indicate that participation in the programme had a…

  6. Efficacy of Gd-DTPA-enhanced MRI in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    The cabability of magnetic resonance (MR) imaging to detect tissue characterization or myocardial degeneration process of the hypertrophied myocardium was evaluated in 15 patients with hypertrophic cardiomyopathy. T1-weighted MR images were obtained with a 1.5 T MR unit by using ECG-gated spin-echo techniques. MR images were visually reviewed before and after enhancement of Gd-DTPA. Four patients had an increase in signal intensity mainly in the endocardium of the left ventricular septum on non-enhanced MR images, 3 of whom had widespread high intensity in addition to two-thirds of the wall. Gd-DTPA enhanced-MR images showed high intensity over the whole septum in 5 patients and also in the antero-lateral endocardium in 4 patients. Decreased intensity on non-enhanced MR images, as shown in 4 patients, became clear on enhanced-MR images. According to findings on enhanced-MR images, signal intensity was defined as normal (N), septum (S), and diffuse (D). Patients in Group D tended to be younger and have more frequently family history. Regarding both interventricular septum thickness and left ventricular posterior wall thickness, there was no significant difference among the three groups. Both left ventricular diastolic diameter and left ventricular systolic diameter were significantly larger in Group D than the other two groups. Left ventricular ejection fraction was significantly lower in both Group S and Group D. Widespread abnormal intensity on Gd-DTPA enhanced MR images was associated with findings similar to dilated cardiomyopathy, such as dilated left ventricular lumen and decreased ejection fraction. Gd-DTPA enhanced MR imaging seemed to be useful for visualizing myocardial degeneration in hypertrophic cardiomyopathy.(N.K.)

  7. Enhancement of Radiotherapeutic Efficacy by Paclitaxel-Loaded pH-Sensitive Block Copolymer Micelles

    OpenAIRE

    Seong-Yun Jeong; Doo Sung Lee; Si Yeol Song; Heon Joo Park; Dong-Hoon Jin; Hye Kyung Chung; Jinhyang Choi; Jaesook Park; Joohee Jung; Sung-Jin Park; Min Sang Kim; Eun Kyung Choi

    2012-01-01

    Radiotherapy (RT) is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX), a well-known radiosensitizer, is insoluble in water and needs toxi...

  8. Enhancing elementary-school mathematics teachers' efficacy beliefs: a qualitative action research

    Science.gov (United States)

    Katz, Sara; Stupel, Moshe

    2016-04-01

    Individuals and societies that can use mathematics effectively in this period of rapid changes will have a voice on increasing the opportunities and potentials which can shape their future. This has brought affective characteristics, such as self-efficacy, that affect mathematics achievement into focus of the research. Teacher efficacy refers to the extent to which a teacher feels capable to help students learn, influence students' performance and commitment, and thus plays a crucial role in developing the student in all aspects. In this study, we used two sources of efficacy beliefs, mastery experiences and physiological and emotional states, in an interesting and challenging seven month workshop, as tools to foster teacher efficacy for six elementary-school teachers who were frustrated and wanted to leave their job. Our aim was to study the nature of these teachers' efficacy in order to change it. In this qualitative action research, we used open interviews, non-participant observations and field notes. Results show that these teachers became efficacious, their students' achievements and motivation were enhanced, and the school climate was changed. Qualitative inquiry of this construct sheds light on efficacy beliefs of mathematics teachers. Nurturing teacher efficacy has borne much fruit in the field of mathematics in school.

  9. Enhancement of DNA vaccine efficacy by intracellular targeting strategies.

    Science.gov (United States)

    Freitas, Elisabete Borges; Henriques, Ana Margarida; Fevereiro, Miguel; Prazeres, Duarte Miguel; Monteiro, Gabriel Amaro

    2014-01-01

    Immune response against an encoded antigenic protein can be elicited by including targeting sequences to DNA vaccines that promote protein sorting to processing pathways, related with antigen presentation by major histocompatibility complexes (MHC). Candidate DNA vaccines coding for neuraminidase 3 of the avian influenza virus were designed to encode different sequences that direct the protein to specific cellular compartments such as endoplasmic reticulum (i.e., adenovirus E1A), lysosomes (i.e., LAMP), and the combination of protein targeting to the endoplasmic reticulum and lysosome (i.e., E1A-LAMP). The DNA vaccine prototypes were engineered by biomolecular techniques and subsequently produced in E. coli cells. The biological activity of the vaccines was tested firstly in vitro, in Chinese hamster ovary cells, through flow cytometry and real-time polymerase chain reaction analysis. Then, an essential in vivo study was performed in chickens, in order to evaluate the efficacy of DNA prototype vaccines, by measuring the antibody production by enzyme-linked immunosorbent assay. PMID:24715281

  10. Using an Attribution Support Tool to Enhance the Teacher Efficacy of Student Science Teachers

    Science.gov (United States)

    de Boer, Eveline; Janssen, Fred J. J. M.; van Driel, Jan H.

    2016-04-01

    To increase the teacher efficacy of student teachers, they need positive classroom experiences: mastery experiences. These mastery experiences have to be created by the student teachers themselves. Therefore, student teachers need a tool to better understand problematic teaching experiences and help them create positive classroom experiences. Nine student biology teachers used this attribution support tool when reflecting on multiple lessons taught in classes they considered difficult. They scored their lessons and filled in a teacher efficacy questionnaire after each lesson. The results show that teacher efficacy increased and the number of failures during the lessons decreased; on average, the self-awarded marks per teacher per lesson increased, indicating an increase in mastery experiences. Therefore, the attribution tool seems to be a promising tool for student teachers to enhance their teacher efficacy and to support reflection on problematic teaching experiences.

  11. Enhancing Self-Efficacy and Performance: An Experimental Comparison of Psychological Techniques

    Science.gov (United States)

    Wright, Bradley James; O'Halloran, Paul Daniel; Stukas, Arthur Anthony

    2016-01-01

    Purpose: We assessed how 6 psychological performance enhancement techniques (PETs) differentially improved self-efficacy (SE) and skill performance. We also assessed whether vicarious experiences and verbal persuasion as posited sources of SE (Bandura, 1982) were supported and, further, if the effects of the 6 PETs remained after controlling for…

  12. Student Teaching Enhancement Program (STEP and Preservice Teachers’ Teaching Efficacy in Science

    Directory of Open Access Journals (Sweden)

    Darryl Roy T. Montebon

    2015-06-01

    Full Text Available The present paper discusses the effect of the Student Teaching Enhancement Program (STEP provided to science preservice teachers in a teacher education institute on their teaching efficacy. The STEP is a program that is designed to impact the areas that influence preservice teachers’ teaching efficacy. Teaching efficacy is an important construct that should be enriched among teachers since the teachers’ belief on their ability to teach significantly affects their performance in the classroom. The STEP has been conducted for a semester and a program evaluation came after. To determine the level of teaching efficacy of the participants they were asked to answer a teaching efficacy survey adopted from the Ohio State Teacher Efficacy Scale developed by Moran and Hoy (2001. The data collected has been subjected to descriptive statistical measures to determine the effect of STEP. Also, an inferential measure was done to compare if the said effects vary by gender and major. Implications of STEP on teacher education program were also discussed.

  13. Enhancement of Radiotherapeutic Efficacy by Paclitaxel-Loaded ph-Sensitive Block Copolymer Micelles

    International Nuclear Information System (INIS)

    Radiotherapy (RT) is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX), a well-known radiosensitizer, is insoluble in water and needs toxic solvent like Cremophor EL. Nano materials in drug delivery systems have been utilized for improving the drawbacks of anti-cancer drugs. Solubilization, tumor accumulation, and toxicity attenuation of drug by nano materials are suitable for enhancement of radiotherapeutic efficacy. In this study, PTX was incorporated into ph-sensitive block copolymer micelle (psm-PTX), polyethylene glycol-graft-poly(β-amino ester), and pre clinically evaluated for its effect on RT. The size of psm-PTX was 125. 4.4±nm at ph 7.4. psm-PTX released PTX rapidly in the acidic condition (ph 6.5), while it was reasonably stable in the physiologic condition (ph 7.4). The clonogenic assay showed that psm-PTX greatly sensitized human non-small-cell lung cancer A549 cells to radiation. In the xenograft tumor model, the combination of psm-PTX and radiation significantly delayed the tumor growth. These results demonstrated the feasibility of psm-PTX to enhance the chemo radiotherapeutic efficacy.

  14. Enhancement of Radiotherapeutic Efficacy by Paclitaxel-Loaded pH-Sensitive Block Copolymer Micelles

    Directory of Open Access Journals (Sweden)

    Joohee Jung

    2012-01-01

    Full Text Available Radiotherapy (RT is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX, a well-known radiosensitizer, is insoluble in water and needs toxic solvent like Cremophor EL. Nanomaterials in drug delivery systems have been utilized for improving the drawbacks of anti-cancer drugs. Solubilization, tumor accumulation, and toxicity attenuation of drug by nanomaterials are suitable for enhancement of radiotherapeutic efficacy. In this study, PTX was incorporated into pH-sensitive block copolymer micelle (psm-PTX, polyethylene glycol-graft-poly(β-amino ester, and preclinically evaluated for its effect on RT. The size of psm-PTX was 125.7±4.4 nm at pH 7.4. psm-PTX released PTX rapidly in the acidic condition (pH 6.5, while it was reasonably stable in the physiologic condition (pH 7.4. The clonogenic assay showed that psm-PTX greatly sensitized human non-small-cell lung cancer A549 cells to radiation. In the xenograft tumor model, the combination of psm-PTX and radiation significantly delayed the tumor growth. These results demonstrated the feasibility of psm-PTX to enhance the chemoradiotherapeutic efficacy.

  15. Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Joohee [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of); Park, Sung-Jin [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium (Singapore); Chung, Hye Kyung [Center for Development and Commercialization of Anti-cancer Therapeutics, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kang, Hye-Won; Lee, Sa-Won; Seo, Min Hyo [Department of Parenteral Delivery Program, Samyang Pharmaceuticals R and D, Daejeon (Korea, Republic of); Park, Heon Joo [Department of Microbiology, College of Medicine, Inha University, Inchon (Korea, Republic of); Song, Si Yeol [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jeong, Seong-Yun, E-mail: syj@amc.seoul.kr [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Kyung, E-mail: ekchoi@amc.seoul.kr [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of)

    2012-09-01

    Purpose: To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. Methods and Materials: The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR). Results: The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice. Conclusions: We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.

  16. Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. Methods and Materials: The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR). Results: The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice. Conclusions: We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.

  17. The health-enhancing efficacy of Zumba® fitness: An 8-week randomised controlled study.

    Science.gov (United States)

    Domene, Pablo A; Moir, Hannah J; Pummell, Elizabeth; Knox, Allan; Easton, Chris

    2016-08-01

    The purpose of this study was to gain a holistic understanding of the efficacy of Zumba® fitness in a community-recruited cohort of overweight and physically inactive women by evaluating (i) its physiological effects on cardiovascular risk factors and inflammatory biomarkers and (ii) its mental health-enhancing effects on factors of health-related quality of life (HRQoL). Participants were randomly assigned to either engagement in one to two 1 h classes of Zumba® fitness weekly (intervention group; n = 10) or maintenance of habitual activity (control group; n = 10). Laboratory assessments were conducted pre- (week 0) and post-intervention (week 8) with anthropometric, physiological, inflammatory and HRQoL data collected. In the intervention group, maximal oxygen uptake significantly increased (P psychosocial health promotion context, our data suggest that Zumba® fitness is indeed an efficacious health-enhancing activity for adults. PMID:26571136

  18. Social Norms Information Enhances the Efficacy of an Appearance-based Sun Protection Intervention

    OpenAIRE

    Kulik, James A.; Butler, Heather; Gerrard, Meg; Gibbons, Frederick X.; Mahler, Heike

    2008-01-01

    This experiment examined whether the efficacy of an appearance-based sun protection intervention could be enhanced by the addition of social norms information. Southern California college students (N=125, predominantly female) were randomly assigned to either an appearance-based sun protection intervention-that consisted of a photograph depicting underlying sun damage to their skin (UV photo) and information about photoaging or to a control condition. Those assigned to the intervention were f...

  19. Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells

    OpenAIRE

    Su, Hao; Zhang, Pengcheng; Cheetham, Andrew G.; Koo, Jin Mo; Lin, Ran; Masood, Asad; Schiapparelli, Paula; Quiñones-Hinojosa, Alfredo; Cui, Honggang

    2016-01-01

    Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubi...

  20. Color rendering ability and luminous efficacy enhancements in white light-emitting diodes

    Science.gov (United States)

    Mirhosseini, Roya; Schubert, Martin; Chhajed, Sameer; Cho, Jaehee; Kim, Jong Kyu; Schubert, E. Fred

    2009-08-01

    There exists a fundamental trade-off relation between color rendering index (CRI) and luminous efficacy; in other words, improvements in one are generally detrimental to the other. We analyze and demonstrate through simulation that phosphor-converted white LEDs with dual-blue emitting active regions, as opposed to single-blue emitting active regions, significantly enhance color rendering ability while maximizing the output luminous flux. The improvements are achieved over a broad range of correlated color temperatures.

  1. Amorphous Silica Based Nanomedicine with Safe Carrier Excretion and Enhanced Drug Efficacy

    Science.gov (United States)

    Zhang, Silu

    With recent development of nanoscience and nanotechnology, a great amount of efforts have been devoted to nanomedicine development. Among various nanomaterials, silica nanoparticle (NP) is generally accepted as non-toxic, and can provide a versatile platform for drug loading. In addition, the surface of the silica NP is hydrophilic, being favorable for cellular uptake. Therefore, it is considered as one of the most promising candidates to serve as carriers for drugs. The present thesis mainly focuses on the design of silica based nanocarrier-drug systems, aiming at achieving safe nanocarrier excretion from the biological system and enhanced drug efficacy, which two are considered as most important issues in nanomedicine development. To address the safe carrier excretion issue, we have developed a special type of selfdecomposable SiO2-drug composite NPs. By creating a radial concentration gradient of drug in the NP, the drug release occurred simultaneously with the silica carrier decomposition. Such unique characteristic was different from the conventional dense SiO2-drug NP, in which drug was uniformly distributed and can hardly escape the carrier. We found that the controllable release of the drug was primarily determined by diffusion, which was caused by the radial drug concentration gradient in the NP. Escape of the drug molecules then triggered the silica carrier decomposition, which started from the center of the NP and eventually led to its complete fragmentation. The small size of the final carrier fragments enabled their easy excretion via renal systems. Apart from the feature of safe carrier excretion, we also found the controlled release of drugs contribute significantly to the drug efficacy enhancement. By loading an anticancer drug doxorubicin (Dox) to the decomposable SiO 2-methylene blue (MB) NPs, we achieved a self-decomposable SiO 2(MB)-Dox nanomedicine. The gradual escape of drug molecules from NPs and their enabled cytosolic release by optical

  2. Efficacy of gadolinium enhanced MR imaging for the diagnosis of Legg-Calve-Perthes disease

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the efficacy of gadolinium enhanced MR imaging for making the diagnosis of Legg-Calve-Perthes (LCP) disease. We studied the gadolinium enhanced MR images of 14 hips in 12 children who had the diagnosis of LCP disease. We retrospectively analyzed the extent of necrosis, the epiphyseal revascularization pathways and the metaphyseal changes. The absence of enhancement on gadolinium enhanced MRI was noted in all cases of LCP disease. Diffuse absence of enhancement was observed in 9 femoral epiphyses. Two of them showed normal bone marrow signal intensity on the T1 and T1-weighted images. Focal absence of enhancement was observed in 5 femoral epiphyses. Enhanced MRI showed better epiphyseal revascularization in the lateral column (five cases), in the lateral and medial columns (four cases) and in the transphyseal pathway (three cases). Metaphyseal change was observed in two cases. Gadolinium enhanced MRI allows detection of LCP disease and an accurate analysis of the different revascularization patterns, and this helpful for predicting the prognosis

  3. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy. PMID:20136435

  4. Gene therapy delivery of endostatin enhances the treatment efficacy of radiation

    International Nuclear Information System (INIS)

    Background and purpose: To evaluate whether sustained expression of mouse endostatin by adeno-associated virus (AAV)-mediated gene transfer can enhance the treatment efficacy of ionizing radiation. Materials and methods: Mouse endostatin was cloned into recombinant AAV (rAAV) under the control of CMV β-actin promoter. Recombinant mouse endostatin expressed via AAV gene transfer was tested for biological activity in endothelial cells. The impact of elevated serum levels of endostatin on tumor-induced angiogenesis was evaluated using an in vivo angiogenesis assay. The anti-tumor efficacy of combining rAAV-mediated endostatin delivery with radiation was evaluated in a human colorectal tumor model (HT29). Results: Recombinant mouse endostatin expressed through an AAV vector (rAAV-mEndo) inhibited endothelial cell proliferation (by 40-45%) and migration (by 22-33%). Intramuscular injection of rAAV-mEndo (1x109 i.u.) led to a sustained serum endostatin level of ∼500 ng/ml. Compared to control animals this endostatin level was sufficient to inhibit tumor cell-induced vessel formation (37 vs. 28.5, P3, 21 vs. 34.5 days, P3 (radiation, 34 days; endostatin plus radiation, 50 days, P<0.05). Conclusion: The delivery of endostatin via rAAV vectors may provide an effective means of enhancing the anti-tumor efficacy of radiation therapy

  5. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    International Nuclear Information System (INIS)

    Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin

  6. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Kim Sung-Ho

    2009-03-01

    Full Text Available Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W. reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

  7. Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques.

    Science.gov (United States)

    Kalaiselvan, R; Mohanta, G P; Madhusudan, S; Manna, P K; Manavalan, R

    2007-08-01

    The objective of this study was to improve the oral bioavailability and therapeutic efficacy of albendazole (ABZ) employing solid dispersion and cyclodextrin complexation techniques. Solid dispersion (dispersion) was prepared using ABZ and polyvinylpyrrolidone (PVP) polymer (1:1 weight ratio). Ternary inclusion complex (ternary complex) was prepared using ABZ, hydroxypropyl beta-cyclodextrin (HPbetaCD) and L-tartaric acid (1:1:1 molar ratio). In rabbits with high gastric acidity (gastric pH approximately 1), ternary complex and solid dispersion showed a bioavailability enhancement of 3.2 and 2.4 fold respectively, compared to a commercial suspension (p 5) caused a 62% reduction in AUC (area under the plasma level curve) for the commercial suspension, whereas the reduction in case of PVP dispersion and ternary complex was only 43% and 37% respectively. The rapid absorption of the drug from solid dispersion and ternary complex was reflected in improved anthelmintic efficacy against the systemic phases of Trichinella spiralis. The ternary complex was significantly more efficient than solid dispersion and exhibited the highest larvicidal activity (90%) at a dose of 50 mg x kg(-1) (p < 0.05). These results suggest that the bioavailability and therapeutic efficacy of the ternary complex might be high even if there is a great variation in the gastric pH. PMID:17867556

  8. Enhancement of the anti-damping spin torque efficacy of platinum by interface modification

    International Nuclear Information System (INIS)

    We report a strong enhancement of the efficacy of the spin Hall effect (SHE) of Pt for exerting anti-damping spin torque on an adjacent ferromagnetic layer by the insertion of ≈0.5 nm layer of Hf between a Pt film and a thin, ≤2 nm, Fe60Co20B20 ferromagnetic layer. This enhancement is quantified by measurement of the switching current density when the ferromagnetic layer is the free electrode in a magnetic tunnel junction. The results are explained as the suppression of spin pumping through a substantial decrease in the effective spin-mixing conductance of the interface, but without a concomitant reduction of the ferromagnet's absorption of the SHE generated spin current

  9. Gap junction enhancer increases efficacy of cisplatin to attenuate mammary tumor growth.

    Directory of Open Access Journals (Sweden)

    Stephanie N Shishido

    Full Text Available Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. Mice were implanted with estradiol-17ß (1.7 mg/pellet before the injection of 1×10⁷ T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control, cisplatin (3.5 mg/kg, PQ (25 mg/kg, or a combining treatment of cisplatin and PQ. Cisplatin alone decreased mammary tumor growth by 85% while combinational treatment of cisplatin and PQ1 or PQ7 showed an additional reduction of 77% and 22% of tumor growth after 7 treatments at every 2 days, respectively. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and cisplatin was seen compared to cisplatin alone. We have showed for the first time an increase in the efficacy of antineoplastic drugs through a combinational treatment with PQs, a specific class of gap junction enhancers.

  10. Folate-conjugated beta-cyclodextrin-based polymeric micelles with enhanced doxorubicin antitumor efficacy.

    Science.gov (United States)

    Zhang, Lu; Lu, Jiafei; Jin, Yangmin; Qiu, Liyan

    2014-10-01

    In order to enhance the antitumor effects of doxorubicin (DOX), a novel micellar vector with high DOX loading and tumor targeting function based on folate-conjugated amphiphilic copolymer folate-poly(ethylene glycol)-poly(d,l-lactide)-β-cyclodextrin (FA-PEL-CD) was constructed. Cytotoxicity and cellular uptake experiments were performed in HeLa, KB, and A549 cell lines expressing different amounts of folate receptors in order to evaluate the targeting effect of the folate modification. The antitumor experiments performed in a KB cell-xenografted nude mouse model showed that the treatment with 10mg/kg DOX loaded FA-PEL-CD micelles achieved approximately 86% of tumor growth inhibition compared to the control. Ex vivo fluorescence imaging experiments and histological examination confirmed that folate modification can enhance the antitumorigenesis efficacy and reduce the cardiotoxicity of DOX. These results suggest that FA-PEL-CD copolymer-based micelles are promising nanocarriers for targeted doxorubicin delivery, with improved antitumor efficacy and reduced toxicity in normal tissues. PMID:25058857

  11. Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas.

    Science.gov (United States)

    Jiang, Hongchi; Meng, Qinghui; Tan, Hongtao; Pan, Shangha; Sun, Bei; Xu, Ruian; Sun, Xueying

    2007-07-15

    Transcatheter arterial embolization (TAE) is a well-established technique for unresectable hepatic malignancies. However, TAE can temporally halt the growth of hepatic tumors by blocking their arterial supply, but often tumors rapidly develop collateral blood vessels via angiogenesis. We have previously demonstrated that intraportal delivery of adeno-associated viral particles expressing angiostatin leads to long-term expression of angiostatin capable of inhibiting angiogenesis and suppressing the outgrowth of tumors in the liver. Thus, we hypothesize that adeno-associated virus (AAV)-mediated antiangiogenic therapy could enhance the efficacy of TAE to combat liver cancers. To achieve this objective, we engineered a recombinant AAV vector encoding rat angiostatin. Intraportal delivery of this vector led to long term and stable transgenic expression of angiostatin locally in rat hepatocytes and suppressed the growth of CBRH7919 hepatocellular carcinomas established in rat livers by inhibiting formation of neovessels. Although TAE therapy led to necrosis of liver tumors and suppressed their growth, the neovessels of tumors were rapidly reformed 3 weeks after TAE. However, intraportal injection of AAV-angiostatin inhibited the angiogenesis stimulated by TAE, synergized with TAE in suppressing growth of tumors established in livers and prolonged the survival of rats. In conclusion, these encouraging results warrant future investigation of the use of antiangiogenic therapy for enhancing the therapeutic efficacy of TAE to treat unresectable liver cancers. PMID:17330237

  12. Quantum dots as enhancers of the efficacy of bacterial lethal photosensitization

    Science.gov (United States)

    Narband, N.; Mubarak, M.; Ready, D.; Parkin, I. P.; Nair, S. P.; Green, M. A.; Beeby, A.; Wilson, M.

    2008-11-01

    Because of the increasing resistance of bacteria to antibiotics there is considerable interest in light-activated antimicrobial agents (LAAAs) as alternatives to antibiotics for treating localized infections. The purpose of this study was to determine whether CdSe/ZnS quantum dots (QD) could enhance the antibacterial activity of the LAAA, toluidine blue O (TBO). Suspensions of Staphylococcus aureus and Streptococcus pyogenes were exposed to white light (3600 lux) and TBO (absorbance maximum = 630 nm) in the presence and absence of 25 nm diameter QD (emission maximum = 627 nm). When the TBO:QD ratio was 2667:1, killing of Staph. aureus was enhanced by 1.72log10 units. In the case of Strep. pyogenes, an enhanced kill of 1.55log10 units was achieved using TBO and QD in the ratio 267:1. Singlet oxygen and fluorescence measurements showed that QD suppress the formation of singlet oxygen from TBO and that QD fluorescence is significantly quenched in the presence of TBO (70-90%). Enhanced killing appears to be attributable to a non-Förster resonance energy transfer mechanism, whereby the QD converts part of the incident light to the absorption maximum for TBO; hence more light energy is harvested, resulting in increased concentrations of bactericidal radicals. QD may, therefore, be useful in improving the efficacy of antimicrobial photodynamic therapy.

  13. Quantum dots as enhancers of the efficacy of bacterial lethal photosensitization

    International Nuclear Information System (INIS)

    Because of the increasing resistance of bacteria to antibiotics there is considerable interest in light-activated antimicrobial agents (LAAAs) as alternatives to antibiotics for treating localized infections. The purpose of this study was to determine whether CdSe/ZnS quantum dots (QD) could enhance the antibacterial activity of the LAAA, toluidine blue O (TBO). Suspensions of Staphylococcus aureus and Streptococcus pyogenes were exposed to white light (3600 lux) and TBO (absorbance maximum = 630 nm) in the presence and absence of 25 nm diameter QD (emission maximum = 627 nm). When the TBO:QD ratio was 2667:1, killing of Staph. aureus was enhanced by 1.72log10 units. In the case of Strep. pyogenes, an enhanced kill of 1.55log10 units was achieved using TBO and QD in the ratio 267:1. Singlet oxygen and fluorescence measurements showed that QD suppress the formation of singlet oxygen from TBO and that QD fluorescence is significantly quenched in the presence of TBO (70-90%). Enhanced killing appears to be attributable to a non-Foerster resonance energy transfer mechanism, whereby the QD converts part of the incident light to the absorption maximum for TBO; hence more light energy is harvested, resulting in increased concentrations of bactericidal radicals. QD may, therefore, be useful in improving the efficacy of antimicrobial photodynamic therapy.

  14. Efficacies of stable manganese for enhancing the elimination of incorporated manganese-54 in mice

    International Nuclear Information System (INIS)

    Efficacies of intraperitoneal injection of stable manganese for enhancing the elimination of incorporated 54Mn was studied in mice. At the start of the experiment, each mouse was given 37 kBq of 54Mn and initial whole-body radioactivities were measured. Forty-eight hours after the injection, mice were given intraperitoneally a single dose of stable manganese at 0.3, 1.0, 3.0 and 10 mg/kg, respectively. Then whole-body retentions and principal organ distributions were measured at suitable intervals. Whole-body retentions of 54Mn decreased markedly following the stable manganese injection, and the efficacies for elimination were estimated to be 45.3% for 0.3 mg/kg, 59.6% for 1.0 mg/kg, 71.4% for 3.0 mg/kg and 78.0% for 10 mg/kg. The substitution rates of incorporated 54Mn for the injected stable manganese were 61.5, 70.8, 79.5 and 83.7%, respectively, suggesting that most of the manganese exists in free or exchangeable state in the body. The concentrations of 54Mn in organs also decreased by stable manganese injection, however, the efficacies for elimination varied with organs. It was generally effective in the soft tissues, and it was ineffective in the bone. In conclusion, intraperitoneal injection of stable manganese was very effective to eliminate the incorporated 54Mn and it could reduce the risk of possible future biological effects. (author)

  15. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers.

    Science.gov (United States)

    Fuchs, Hendrik; Weng, Alexander; Gilabert-Oriol, Roger

    2016-01-01

    The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments. PMID:27376327

  16. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers

    Directory of Open Access Journals (Sweden)

    Hendrik Fuchs

    2016-07-01

    Full Text Available The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments.

  17. Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy.

    Science.gov (United States)

    Ahmad, Tanveer; Mukherjee, Shravani; Pattnaik, Bijay; Kumar, Manish; Singh, Suchita; Kumar, Manish; Rehman, Rakhshinda; Tiwari, Brijendra K; Jha, Kumar A; Barhanpurkar, Amruta P; Wani, Mohan R; Roy, Soumya S; Mabalirajan, Ulaganathan; Ghosh, Balaram; Agrawal, Anurag

    2014-05-01

    There is emerging evidence that stem cells can rejuvenate damaged cells by mitochondrial transfer. Earlier studies show that epithelial mitochondrial dysfunction is critical in asthma pathogenesis. Here we show for the first time that Miro1, a mitochondrial Rho-GTPase, regulates intercellular mitochondrial movement from mesenchymal stem cells (MSC) to epithelial cells (EC). We demonstrate that overexpression of Miro1 in MSC (MSCmiro(Hi)) leads to enhanced mitochondrial transfer and rescue of epithelial injury, while Miro1 knockdown (MSCmiro(Lo)) leads to loss of efficacy. Treatment with MSCmiro(Hi) was associated with greater therapeutic efficacy, when compared to control MSC, in mouse models of rotenone (Rot) induced airway injury and allergic airway inflammation (AAI). Notably, airway hyperresponsiveness and remodeling were reversed by MSCmiro(Hi) in three separate allergen-induced asthma models. In a human in vitro system, MSCmiro(Hi) reversed mitochondrial dysfunction in bronchial epithelial cells treated with pro-inflammatory supernatant of IL-13-induced macrophages. Anti-inflammatory MSC products like NO, TGF-β, IL-10 and PGE2, were unchanged by Miro1 overexpression, excluding non-specific paracrine effects. In summary, Miro1 overexpression leads to increased stem cell repair. PMID:24431222

  18. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

    Science.gov (United States)

    Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

    2006-08-15

    We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines. PMID:16888001

  19. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Larson JL

    2014-10-01

    Full Text Available Janet L Larson,1,2 Margaret K Covey,2 Mary C Kapella,2 Charles G Alex,3,4 Edward McAuley,5 1Division of Acute, Critical and Long-Term Care Programs, School of Nursing, University of Michigan, Ann Arbor, MI, 2Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, 3Division of Pulmonary and Critical Care Medicine, Edward Hines Jr VA Hospital, Hines, IL, 4Advocate Christ Medical Center, Oaklawn, IL, 5Department of Kinesiology and Community Health, College of Applied Health Sciences, University of Illinois Urbana-Champagne, Urbana, IL, USA Background: People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. Methods: In this randomized controlled trial, subjects were assigned to: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR, health education with upper body resistance training (ED-UBR, or health education with gentle chair exercises (ED-Chair. Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Results: Differences were observed in light physical activity (LPA after 4 months of training, time by group interaction effect (P=0.045. The SE-UBR group increased time spent in

  20. Superselective Particle Embolization Enhances Efficacy of Radiofrequency Ablation: Effects of Particle Size and Sequence of Action

    International Nuclear Information System (INIS)

    Purpose. To evaluate the effects of particle size and course of action of superselective bland transcatheter arterial embolization (TAE) on the efficacy of radiofrequency ablation (RFA). Methods. Twenty pigs were divided into five groups: group 1a, 40-μm bland TAE before RFA; group 1b, 40-μm bland TAE after RFA; group 2a, 250-μm bland TAE before RFA; group 2b, 250-μm bland TAE after RFA and group 3, RFA alone. A total of 40 treatments were performed with a combined CT and angiography system. The sizes of the treated zones were measured from contrast-enhanced CTs on days 1 and 28. Animals were humanely killed, and the treated zones were examined pathologically. Results. There were no complications during procedures and follow-up. The short-axis diameter of the ablation zone in group 1a (mean ± standard deviation, 3.19 ± 0.39 cm) was significantly larger than in group 1b (2.44 ± 0.52 cm; P = 0.021), group 2a (2.51 ± 0.32 cm; P = 0.048), group 2b (2.19 ± 0.44 cm; P = 0.02), and group 3 (1.91 ± 0.55 cm; P 3). At histology, 40-μm microspheres were observed to occlude smaller and more distal arteries than 250-μm microspheres. Conclusion. Bland TAE is more effective before RFA than postablation embolization. The use of very small 40-μm microspheres enhances the efficacy of RFA more than the use of larger particles.

  1. Usefulness of contrast-enhanced ultrasonography in determining treatment efficacy and outcome after pancreatic cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate if contrast-enhanced ultrasono-graphy (CE-US) is useful for determining treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy by assessing changes in intratumor hemodynamics using CE-US with a contrast agent.METHODS: The subjects were 34 patients with unresectable advanced pancreatic cancer treated by chemotherapy. CE-US was assessed after every treatment (course) completion under the same conditions, and patients were divided into two groups according to the intratumor enhancement pattern: Vascular rich (R) group and vascular poor (P) group. RESULTS: After the second course of treatment, R group in intratumor hemodynamics had 18 patients, and P group had 16 patients. The reduction rates of serum CA19-9 level after chemotherapy which decreased to half or less of the baseline level were 2/15 (0.1%) in P group, but 11/16 (69%) in R group (P = 0.006). When the mean number of courses of chemotherapy and outcome were compared, P group had a mean number of courses of 4.9 (R group, 10.2) and mean survival time (MST) of 246 d (R group, 402 d), showing that outcome was significantly better in R group (P = 0.006).CONCLUSION: CE-US revealed that the change in intratumor blood flow correlated with both serum CA19-9 level and outcome. Patients with serum CA19-9 that decreased to less than half the baseline level, and patients with an abundant intratumor blood flow, had a significantly better outcome. Thus, CE-US is tentially useful for evaluating treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy.

  2. Mechanisms mediating enhanced neutralization efficacy of staphylococcal enterotoxin B by combinations of monoclonal antibodies.

    Science.gov (United States)

    Dutta, Kaushik; Varshney, Avanish K; Franklin, Matthew C; Goger, Michael; Wang, Xiaobo; Fries, Bettina C

    2015-03-13

    Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations. PMID:25572397

  3. Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy

    Science.gov (United States)

    Yang, Lei; Wang, Zheran; Wang, Ju; Jiang, Weihua; Jiang, Xuewei; Bai, Zhaoshi; He, Yunpeng; Jiang, Jianqi; Wang, Dongkai; Yang, Li

    2016-03-01

    Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared

  4. Using on-line video clips to enhance self-efficacy toward dealing with difficult situations among nursing students.

    Science.gov (United States)

    McConville, Sally A; Lane, Andrew M

    2006-04-01

    The aim of the study was twofold. The first aim was to develop on-line video clip material that showed examples of nurses dealing with potentially difficult and delicate patient groups. The second aim was to evaluate the effectiveness of video clip materials for enhancing nursing student's self-efficacy to effectively communicate with the type of patients described above. The production of contextually relevant video clip material involved the identification of relevant material based on real experiences, writing appropriate scripts, recruiting actors, recording the performances and producing them in a form that could be accessed on-line. Self-report questionnaires were used to assess the effectiveness of video clip material. Level 1 (n = 145) nursing students completed a self-efficacy measure that assessed confidence to deal with situations such as breaking news of death, working with children, people with disability and aggressive behaviour at the start and the end of the module. Results indicated that student's self-efficacy increased noticeably over the course of the module. Differences between increases in self-efficacy attributed to watching videos or attending lectures were marginal. Findings suggest that using video clips that show students effectively coping with adverse situations provide an effective teaching approach for enhancing self-efficacy. Future research is needed to test the extent to which self-efficacy measures relate with nursing performance. PMID:16300862

  5. Engineering of hollow mesoporous silica nanoparticles for remarkably enhanced tumor active targeting efficacy.

    Science.gov (United States)

    Chen, Feng; Hong, Hao; Shi, Sixiang; Goel, Shreya; Valdovinos, Hector F; Hernandez, Reinier; Theuer, Charles P; Barnhart, Todd E; Cai, Weibo

    2014-01-01

    Hollow mesoporous silica nanoparticle (HMSN) has recently gained increasing interests due to their tremendous potential as an attractive nano-platform for cancer imaging and therapy. However, possibly due to the lack of efficient in vivo targeting strategy and well-developed surface engineering techniques, engineering of HMSN for in vivo active tumor targeting, quantitative tumor uptake assessment, multimodality imaging, biodistribution and enhanced drug delivery have not been achieved to date. Here, we report the in vivo tumor targeted positron emission tomography (PET)/near-infrared fluorescence (NIRF) dual-modality imaging and enhanced drug delivery of HMSN using a generally applicable surface engineering technique. Systematic in vitro and in vivo studies have been performed to investigate the stability, tumor targeting efficacy and specificity, biodistribution and drug delivery capability of well-functionalized HMSN nano-conjugates. The highest uptake of TRC105 (which binds to CD105 on tumor neovasculature) conjugated HMSN in the 4T1 murine breast cancer model was ~10%ID/g, 3 times higher than that of the non-targeted group, making surface engineered HMSN a highly attractive drug delivery nano-platform for future cancer theranostics. PMID:24875656

  6. Mitochondria and nuclei dual-targeted heterogeneous hydroxyapatite nanoparticles for enhancing therapeutic efficacy of doxorubicin.

    Science.gov (United States)

    Xiong, Hui; Du, Shi; Ni, Jiang; Zhou, Jianping; Yao, Jing

    2016-07-01

    Dual-targeted nanoparticles have been increasingly used to realize greater anti-proliferation effect by attacking double key sites of tumor cells. In order to retain nuclei inhibition effect and enhance DOX-induced apoptosis by mitochondrial pathway simultaneously, hyaluronic acid (HA) modified hydroxyapatite (HAP) nanoparticles (HAP-HA), the functional calcium-based tumor targeting nanoparticles, have been developed. In this nanosystem, HA acts as an active tumor-targeting ligand to bind the CD44 receptors which are overexpressed on the surface of tumor cells while HAP can load and deliver DOX to both nuclei and mitochondria of tumor cells. In this study, DOX-loaded HAP-HA nanoparticles (DOX/HAP-HA) exhibited satisfactory drug loading efficiency which was up to 214.55 ± 51.05 μg mg(-1) and showed a uniform nano-scaled particle size. The mitochondrial and nuclei targetability of DOX/HAP-HA was confirmed by confocal laser scanning microscopy analyses. Besides, western blot assay demonstrated that DOX/HAP-HA could markedly enhance mitochondrial cytochrome C leakage and thereby activate apoptotic cascade associated with it. In addition, in vivo anti-tumor efficacy and toxicity evaluation of DOX/HAP-HA indicated that DOX/HAP-HA was more effective and less harmful compared to other groups. DOX/HAP-HA might be a new promising targeted delivery system for effective cancer therapy. PMID:27105438

  7. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis.

    Science.gov (United States)

    Jain, S K; Gill, M S; Pawar, H S; Suresh, Sarasija

    2014-09-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (Parthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin. PMID:25425755

  8. Novel curcumin diclofenac conjugate enhanced curcumin bioavailability and efficacy in streptococcal cell wall-induced arthritis

    Directory of Open Access Journals (Sweden)

    S K Jain

    2014-01-01

    Full Text Available Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01 alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  9. The Development of a Cultural-Based Educational Program to Enhance Breast Self-Examination (BSE Self-Efficacy

    Directory of Open Access Journals (Sweden)

    Juanita Juanita

    2012-08-01

    Full Text Available Purpose: To develop the educational program which is appropriate with Islamic culture in order to enhance BSE self-efficacy of nursing students and thus promote BSE practice. Method: This study is a development research study which is consisting of three phases including: 1 reviewing several existing BSE educational programs; 2 program design based on SCT and Islamic culture; and 3 program validation by three experts. Result: Based on previous studies, the most appropriate theory to enhance self-efficacy was Social Cognitive Theory (SCT because this theory provides several strategies to increase the self-efficacy. Further, the program that used Islamic culture was more appropriate to increase BSE practice among Muslim women. As a result, the newly developed program was developed used SCT and Islamic culture. This program was comprised of four sessions including: 1 exploring Islamic mandate on prevention and individual responsibility in health promotion, and culture-related beliefs toward BSE, 2 health education by conducting lecturing session and watching a video about BSE procedures, 3 BSE training activities including BSE demonstration and return demonstration, 4 follow-up by conducting a meeting. Conclusion: The cultural-based educational program for enhancing BSE self-efficacy and promoting BSE is a program using multifaceted methods. It designed based on a review of the literature from previous studies and were supported by research findings on experimental studies in other population. Keywords: Cultural, Educational program development, Breast self-examination, Self-efficacy.

  10. Enhancing self-efficacy improves episodic future thinking and social-decision making in combat veterans with posttraumatic stress disorder.

    Science.gov (United States)

    Brown, Adam D; Kouri, Nicole A; Rahman, Nadia; Joscelyne, Amy; Bryant, Richard A; Marmar, Charles R

    2016-08-30

    Posttraumatic Stress Disorder (PTSD) is associated with maladaptive changes in self-identity, including impoverished perceived self-efficacy. This study examined if enhancing perceptions of self-efficacy in combat veterans with and without symptoms of PTSD promotes cognitive strategies associated with positive mental health outcomes. Prior to completing a future thinking and social problem-solving task, sixty-two OEF/OIF veterans with and without symptoms of PTSD were randomized to either a high self-efficacy (HSE) induction in which they were asked to recall three autobiographical memories demonstrating self-efficacy or a control condition in which they recalled any three autobiographical events. An interaction between HSE and PTSD revealed that individuals with symptoms of PTSD in the HSE condition generated future events with more self-efficacious statements than those with PTSD in the control condition, whereas those without PTSD did not differ in self-efficacy content across the conditions. In addition, individuals in the HSE condition exhibited better social problem solving than those in the control condition. Increasing perceptions of self-efficacy may promote future thinking and problem solving in ways that are relevant to overcoming trauma and adversity. PMID:27236589

  11. The Effectiveness of Group Motivational Interviewing Sessions on Enhancing of Addicted Women’s Self-Esteem and Self Efficacy

    Directory of Open Access Journals (Sweden)

    Samireh Dehghani F

    2013-07-01

    Full Text Available Objective: The aim of present research was to study of the effectiveness of motivational interviewing on enhancing of self-esteem and self-efficacy in addicted women who were under therapy. Method: The research method was semi experimental research design namely: pretest-posttest with witness group. The population consisted of all addicted women who were referred to Ayandeh Roshan recovery addiction camp of Isfahan city during summer in 1391. By available sampling, 30 women selected and divided randomly to two experimental and witness groups (N= 15, per group. Experimental group received eight sessions of 90 minutes based on group counseling sessions following motivational interviewing style. For gathering data, Cooper Smith’s self-esteem and general self-efficacy questionnaires administered among two groups. Results: The results indicated the effectiveness of motivational interviewing. Conclusion: It can be concluded that motivational interviewing has had enhancing effect on self-esteem and self-efficacy among experimental group.

  12. Bioavailability and efficacy of a gap junction enhancer (PQ7 in a mouse mammary tumor model.

    Directory of Open Access Journals (Sweden)

    Stephanie N Shishido

    Full Text Available The loss of gap junctional intercellular communication is characteristic of neoplastic cells, suggesting that the restoration with a gap junction enhancer may be a new therapeutic treatment option with less detrimental effects than traditional antineoplastic drugs. A gap junction enhancer, 6-methoxy-8-[(2-furanylmethyl amino]-4-methyl-5-(3-trifluoromethylphenyloxy quinoline (PQ7, on the normal tissue was evaluated in healthy C57BL/6J mice in a systemic drug distribution study. Immunoblot analysis of the vital organs indicates a reduction in Cx43 expression in PQ7-treated animals with no observable change in morphology. Next the transgenic strain FVB/N-Tg(MMTV-PyVT 634Mul/J (also known as PyVT was used as a spontaneous mammary tumor mouse model to determine the biological and histological effects of PQ7 on tumorigenesis and metastasis at three stages of development: Pre tumor, Early tumor, and Late tumor formation. PQ7 was assessed to have a low toxicity through intraperitoneal administration, with the majority of the compound being detected in the heart, liver, and lungs six hours post injection. The treatment of tumor bearing animals with PQ7 had a 98% reduction in tumor growth, while also decreasing the total tumor burden compared to control mice during the Pre stage of development. PQ7 treatment increased Cx43 expression in the neoplastic tissue during Pre-tumor formation; however, this effect was not observed in Late stage tumor formation. This study shows that the gap junction enhancer, PQ7, has low toxicity to normal tissue in healthy C57BL/6J mice, while having clinical efficacy in the treatment of spontaneous mammary tumors of PyVT mice. Additionally, gap junctional intercellular communication and neoplastic cellular growth are shown to be inversely related, while treatment with PQ7 inhibits tumor growth through targeting gap junction expression.

  13. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy

  14. Inspiring Instructional Change in Elementary School Science: The Relationship between Enhanced Self-Efficacy and Teacher Practices

    Science.gov (United States)

    Sandholtz, Judith Haymore; Ringstaff, Cathy

    2014-01-01

    This longitudinal study examined the extent to which teachers' participation in a 3-year professional development program enhanced their self-efficacy and prompted changes in science instruction in the early elementary grades. The study used a mixed-methods design, and included 39 teachers who taught in kindergarten, first grade, or second…

  15. Does computerized working memory training with game elements enhance motivation and training efficacy in children with ADHD?

    NARCIS (Netherlands)

    P.J.M. Prins; S. Dovis; A. Ponsioen; E. ten Brink; S. van der Oord

    2010-01-01

    This study examined the benefits of adding game elements to standard computerized working memory (WM) training. Specifically, it examined whether game elements would enhance motivation and training performance of children with ADHD, and whether it would improve training efficacy. A total of 51 child

  16. Does computerized working memory training with game elements enhance motivation and training efficacy in children with ADHD?

    NARCIS (Netherlands)

    P.J.M. Prins; S. Dovis; A. Ponsioen; E. ten Brink; S. van der Oord

    2011-01-01

    This study examined the benefits of adding game elements to standard computerized working memory (WM) training. Specifically, it examined whether game elements would enhance motivation and training performance of children with ADHD, and whether it would improve training efficacy. A total of 51 child

  17. Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

    Directory of Open Access Journals (Sweden)

    Choi J

    2015-09-01

    Full Text Available Jinhyang Choi,1,2 Eunjung Ko,1 Hye-Kyung Chung,3 Jae Hee Lee,1 Eun Jin Ju,1 Hyun Kyung Lim,4 Intae Park,1 Kab-Sig Kim,5 Joo-Hwan Lee,5 Woo-Chan Son,6 Jung Shin Lee,1,7 Joohee Jung,1,4 Seong-Yun Jeong,1,2 Si Yeol Song,1,8 Eun Kyung Choi1,3,8 1Institute for Innovative Cancer Research, 2Asan Institute for Life Sciences, 3Center for Development and Commercialization of Anti-cancer Therapeutics, 4College of Pharmacy, Duksung Women’s University, 5Bio-Synectics, 6Department of Pathology, 7Department of Internal Medicine, 8Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Abstract: Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX, under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™ technology enabled successful nanoscale particulation of DTX (Nufs-DTX. Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in

  18. Enhancing the efficacy of cisplatin in ovarian cancer treatment – could arsenic have a role

    Directory of Open Access Journals (Sweden)

    Helm C William

    2009-01-01

    Full Text Available Abstract Ovarian cancer affects more than 200,000 women each year around the world. Most women are not diagnosed until the disease has already metastasized from the ovaries with a resultant poor prognosis. Ovarian cancer is associated with an overall 5 year survival of little more than 50%. The mainstay of front-line therapy is cytoreductive surgery followed by chemotherapy. Traditionally, this has been by the intravenous route only but there is more interest in the delivery of intraperitoneal chemotherapy utilizing the pharmaco-therapeutic advantage of the peritoneal barrier. Despite three large, randomized clinical trials comparing intravenous with intraperitoneal chemotherapy showing improved outcomes for those receiving at least part of their chemotherapy by the intraperitoneal route. Cisplatin has been the most active drug for the treatment of ovarian cancer for the last 4 decades and the prognosis for women with ovarian cancer can be defined by the tumor response to cisplatin. Those whose tumors are innately platinum-resistant at the time of initial treatment have a very poor prognosis. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin and will ultimately succumb to the disease. Improving the efficacy of cisplatin could have a major impact in the fight against this disease. Arsenite is an exciting agent that not only has inherent single-agent tumoricidal activity against ovarian cancer cell lines but also multiple biochemical interactions that may enhance the cytotoxicity of cisplatin including inhibition of deoxyribose nucleic acid (DNA repair. In vitro studies suggest that arsenite may enhance the activity of cisplatin in other cell types. Arsenic trioxide is already used clinically to treat acute promyelocytic leukemia demonstrating its safety profile. Further research in ovarian cancer is warranted to define

  19. Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs

    Science.gov (United States)

    Choi, Jinhyang; Ko, Eunjung; Chung, Hye-Kyung; Lee, Jae Hee; Ju, Eun Jin; Lim, Hyun Kyung; Park, Intae; Kim, Kab-Sig; Lee, Joo-Hwan; Son, Woo-Chan; Lee, Jung Shin; Jung, Joohee; Jeong, Seong-Yun; Song, Si Yeol; Choi, Eun Kyung

    2015-01-01

    Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO2), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs. PMID:26457052

  20. Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.

    Directory of Open Access Journals (Sweden)

    Mark S Pearson

    Full Text Available The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1 and IgG(3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1, suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.

  1. Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.

    Science.gov (United States)

    Pearson, Mark S; Pickering, Darren A; McSorley, Henry J; Bethony, Jeffrey M; Tribolet, Leon; Dougall, Annette M; Hotez, Peter J; Loukas, Alex

    2012-01-01

    The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1) and IgG(3) from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic. PMID:22428079

  2. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    Science.gov (United States)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  3. Surface decoration by Spirulina polysaccharide enhances the cellular uptake and anticancer efficacy of selenium nanoparticles

    Directory of Open Access Journals (Sweden)

    Li Y

    2012-02-01

    Full Text Available Fang Yang1*, Quanming Tang1,2*, Xueyun Zhong3, Yan Bai1, Tianfeng Chen1, Yibo Zhang1, Yinghua Li1, Wenjie Zheng11Department of Chemistry, Jinan University, Guangzhou, China; 2South China Seas Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China; 3Department of Pathology, Jinan University, Guangzhou, China*These authors contributed equally to this workAbstract: A simple and solution-phase method for functionalization of selenium nanoparticles (SeNPs with Spirulina polysaccharides (SPS has been developed in the present study. The cellular uptake and anticancer activity of SPS-SeNPs were also evaluated. Monodisperse and homogeneous spherical SPS-SeNPs with diameters ranging from 20 nm to 50 nm were achieved under optimized conditions, which were stable in the solution phase for at least 3 months. SPS surface decoration significantly enhanced the cellular uptake and cytotoxicity of SeNPs toward several human cancer cell lines. A375 human melanoma cells were found extremely susceptible to SPS-SeNPs with half maximal (50% inhibitory concentration value of 7.94 µM. Investigation of the underlying mechanisms revealed that SPS-SeNPs inhibited cancer cell growth through induction of apoptosis, as evidenced by an increase in sub-G1 cell population, deoxyribonucleic acid fragmentation, chromatin condensation, and phosphatidylserine translocation. Results suggest that the strategy to use SPS as a surface decorator could be an effective way to enhance the cellular uptake and anticancer efficacy of nanomaterials. SPS-SeNPs may be a potential candidate for further evaluation as a chemopreventive and chemotherapeutic agent against human cancers.Keywords: selenium nanoparticles, Spirulina polysaccharide, cellular uptake, anticancer, apoptosis

  4. The efficacy of fat suppressed and gadolinium enhanced dynamic MR imaging in pancreatic adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Gabata, Toshifumi [Kanazawa Univ. (Japan). School of Medicine

    1994-12-01

    The efficacy of both fat suppressed T1-weighted imaging (T1WI) and dynamic gadolinium-enhanced MR imaging (dynamic MRI) was compared with conventional MR sequences and dynamic CT in 22 patients with histologically proven pancreatic adenocarcinoma (PAC). In the control group of 30 patients without pancreatic disease, the pancreas was shown as a markedly higher signal intensity on fat suppressed T1WI than on conventional MR sequences. The signal noise ratio (SNR) of the normal pancreas and the contrast noise ratio (CNR) between the normal pancreas and muscle were significantly higher on fat suppressed T1WI than the other MR sequences. In the group of PAC patients without chronic pancreatitis (n=14), CNR between the tumor and the normal pancreas significantly differed among imaging techniques, including fat suppressed T1WI, dynamic MRI, and the other conventional MR sequences. In the group of PAC with chronic pancreatitis (n=8), CNR between the tumor and the associated chronic pancreatitis was remarkably diminished on both fat suppressed T1WI and conventional T1WI; however, it was significantly higher on dynamic MRI than the other pulse sequences. The early phase of dynamic MRI clearly identified the tumors in the group of PAC. The capability of conventional T1WI and dynamic CT to demonstrate peripancreatic tumor extension was significantly higher than that of fat suppressed T1WI. In conclusion, fat suppressed T1WI and dynamic MRI were useful in detecting pancreatic carcinoma. (N.K.).

  5. Enhanced photodynamic efficacy of PLGA-encapsulated 5-ALA nanoparticles in mice bearing Ehrlich ascites carcinoma

    Science.gov (United States)

    Shaker, Maryam N.; Ramadan, Heba S.; Mohamed, Moustafa M.; El khatib, Ahmed M.; Roston, Gamal D.

    2014-10-01

    Nanoparticles (NPs) fabricated from the biodegradable copolymer poly(lactic- co-glycolic acid) (PLGA) were investigated as a drug delivery system to enhance the photodynamic efficacy of 5-aminolevulinic acid (5-ALA) in mice bearing Ehrlich ascites carcinoma. The PLGA-encapsulated 5-ALA NPs were prepared using binary organic solvent diffusion method and characterized in terms of shape and particle size. The in vivo photodynamic efficiency in Ehrlich ascites-bearing mice was studied. The obtained particles were uniform in size with spherical shape of mean size of 249.5 nm as obtained by particle size analyzer and the in vitro release studies demonstrated a controlled release profile of 5-ALA. Tumor-bearing mice injected with PLGA-encapsulated 5-ALA NPs exhibited significantly smaller mean tumor volume, increased tumor growth delay compared with the control group and the group injected with free 5-ALA during the time course of the experiment. Histopathological examination of tumor from mice treated with PLGA-encapsulated 5-ALA NPs showed regression of tumor cells, in contrast to those obtained from mice treated with free 5-ALA. The results indicate that PLGA-encapsulated 5-ALA NPs are a successful delivery system for improving photodynamic activity in the target tissue.

  6. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy

    Directory of Open Access Journals (Sweden)

    K. M. Maheswari

    2014-01-01

    Full Text Available The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs of Amlodipine Besylate (AMLO to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC and methyl cellulose (MC along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30, and sodium lauryl sulphate (SLS as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

  7. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy.

    Science.gov (United States)

    Maheswari, K M; Devineni, Pavan Kumar; Deekonda, Sravanthi; Shaik, Salma; Uppala, Naga Pravallika; Nalluri, Buchi N

    2014-01-01

    The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose (MC) along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30), and sodium lauryl sulphate (SLS) as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w) of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism. PMID:26556197

  8. Enhancing the efficacy of engraftment of cord blood for hematopoietic cell transplantation.

    Science.gov (United States)

    Broxmeyer, Hal E

    2016-06-01

    Clinical cord blood (CB) hematopoietic cell transplantation (HCT) has progressed well since the initial successful CB HCT that saved the life of a young boy with Fanconi anemia. The recipient is alive and well now 28 years out since that first transplant with CB cells from his HLA-matched sister. CB HCT has now been used to treat over 35,000 patients with various malignant and non-malignant disorders mainly using HLA-matched or partially HLA-disparate allogeneic CB cells. There are advantages and disadvantages to using CB for HCT compared to other sources of transplantable hematopoietic stem (HSC) and progenitor (HPC) cells. One disadvantage of the use of CB as a source of transplantable HSC and HPC is the limited number of these cells in a single CB collected, and slower time to neutrophil, platelet and immune cell recovery. This review describes current attempts to: increase the collection of HSC/HPC from CB, enhance the homing of the infused cells, ex-vivo expand numbers of collected HSC/HPC and increase production of the infused CB cells that reach the marrow. The ultimate goal is to manipulate efficiency and efficacy for safe and economical use of single unit CB HCT. PMID:27211041

  9. Enhanced efficacy of CTLA-4 fusion anti-caries DNA vaccines in gnotobiotic hamsters

    Institute of Scientific and Technical Information of China (English)

    Feng ZHANG; Yu-hong LI; Ming-wen FAN; Rong JIA; Qing-an XU; Ji-hua GUO; Fei YU; Qi-wei TIAN

    2007-01-01

    Aim:To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T-lymphocyte.associated antigen 4(CTLA-4)fusion anti-caries DNA vaccines pGJA-P/VAX1,pGJA-P,and non-fusion anti-caries DNA construct pGLUA-P in hamsters.In addition,the ability of CTLA-4 to target pGJA-P/VAX1-encoding antigen to dendritic cells was tested in vitro.Methods:All DNA constructs contain genes encoding the A-P regions of a cell surface protein(PAc) and the glucan binding(GLU) domain of glucosyltransferases(GTFs)of cari-ogenic organism Streptococcus mutans.Human dendritic cells were mixed with the CTLA-4-Ig-GLU-A-P protein expressed by pGJA-P/VAX1-transfected cells and analyzed by flow cytometry.Gnotobiotic hamsters were immunized with anti-caries DNA vaccines by intramuscular injection or intranasal administration.Antibody responses to a representative antigen PAc were assayed by ELlSA,and caries protection was evaluated by Keyes caries scores.Results:A flow cytometric analysis demonstrated that CTLA-4-Ig-GLU-A-P protein was capable of bind-ing to human dendritic cells.pGJA-P/VAX1 and pGJA-P induced significantly higher specific salivary and serum anti-PAc antibody responses than pGLUA-R.Significantly fewet caries lesions were alSO observed in hamsters immunized with pGJA-P/VAX1 and pGJA-p There was no significant difference in the anti-PAC antibody level or caries scores between pGJA-P/VAX1 and pGJA-P-immunized groups.Conclusion:Antigen encoded by CTLA-4 fusion anti-caries DNA vac-cine pGJA-P/VAX1 could specifically bind to human dendritic cells through the interaction of CTLA-4 and B7 molecules.Fusing antigen to CTLA-4 has been proven to greatly enhance the immunogenicity and protective efficacy of anti-caries DNA vaccines.

  10. Depletion of T cell epitopes in lysostaphin mitigates anti-drug antibody response and enhances antibacterial efficacy in vivo

    Science.gov (United States)

    Zhao, Hongliang; Verma, Deeptak; Li, Wen; Choi, Yoonjoo; Ndong, Christian; Fiering, Steven N.; Bailey-Kellogg, Chris; Griswold, Karl E.

    2015-01-01

    SUMMARY The enzyme lysostaphin possesses potent anti-staphylococcal activity and represents a promising antibacterial drug candidate; however, its immunogenicity poses a barrier to clinical translation. Here, structure-based biomolecular design enabled widespread depletion of lysostaphin’s DRB1*0401 restricted T cell epitopes, and resulting deimmunized variants exhibited striking reductions in anti-drug antibody responses upon administration to humanized HLA-transgenic mice. This reduced immunogenicity translated into improved efficacy in the form of protection against repeated challenges with methicillin-resistant Staphylococcus aureus, or MRSA. In contrast, while wild type lysostaphin was efficacious against the initial MRSA infection, it failed to clear subsequent bacterial challenges that were coincident with escalating anti-drug antibody titers. These results extend the existing deimmunization literature, in which reduced immunogenicity and retained efficacy are assessed independently of each other. By correlating in vivo efficacy with longitudinal measures of anti-drug antibody development, we provide the first direct evidence that T cell epitope depletion manifests enhanced biotherapeutic efficacy. PMID:26000749

  11. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    OpenAIRE

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2014-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, im...

  12. Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis

    OpenAIRE

    Hwang, Shen-An; Wilk, Katarzyna M.; Budnicka, Monika; Olsen, Margaret; Bangale, Yogesh A.; Hunter, Robert L.; Kruzel, Marian L.; Actor, Jeffrey K.

    2007-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world’s population. The established vaccine for TB, an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed since 1921. Lactoferrin, an iron binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine, specifically because of previous repor...

  13. Interaction of pre- and post-emergence herbicide treatment on efficacy of different black-grass biotypes with enhanced metabolism

    OpenAIRE

    Petersen, Jan; Olf, Florian

    2014-01-01

    In an outdoor container trial with different resistant black-grass biotypes with enhanced metabolism, efficacy of pre- and post-emergence treatments as well as their sequence was investigated in spring wheat. Weed control success was compared to a susceptible biotype. Results indicate that there are strong interactions between herbicide and black-grass biotypes. As a consequence site specific herbicide strategies corresponding to current herbicide resistance situation can be necessary. If fur...

  14. The essence of staff development for enhancing teachers efficacy in Moses Kotane East area project office / E.M Modisane

    OpenAIRE

    Modisane, E M

    2010-01-01

    The study was about the essence of staff development for enhancing teachers' efficacy in Moses Kotane East Area Project Office. The study sought to answer the following research questions: What is the significance of staff development in schools? Which major factors necessitate staff development in schools? What are the characteristics of an effective staff development initiative? The researcher opted for both qualitative and quantitative research methods. Both the questionn...

  15. How Setting Goals Enhances Learners’ Self-Efficacy Beliefs in Listening Comprehension

    OpenAIRE

    Liliana Ballesteros Muñoz; Silvana Tutistar Jojoa

    2014-01-01

    This article outlines a study that explores the relationship between SMART goal setting (Specific, Measurable, Attainable, Relevant, and Time-based) and learning English in Colombia concerning a foreign language learners’ self-efficacy beliefs in listening. The participants were seventh and ninth grade students of two schools in Bogotá, Colombia. The results revealed that self-efficacy was highly positive when related to goal setting as students were able to set SMART goals to improve their l...

  16. Enhancement of biocontrol efficacy against Botrytis cinerea through the manipulation of nitrogen fertilization of tomato plants

    OpenAIRE

    Abro, Manzoor Ali; Lecompte, François; Bardin, Marc; Duffaud, Magali

    2013-01-01

    Although nitrogen fertilization is known to affect plant susceptibility to certain pathogens, little is known on its possible effect on the efficacy of biological control. In the present study we examined the effect of five levels of NO3- nutrition on the efficacy of two biocontrol agents (Trichoderma harzianum and Microdochium dimerum) to protect pruning wounds of tomato against Botrytis cinerea. Plants were grown for two months in a greenhouse with a soil-less drip-irrigationsystem. Differe...

  17. IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy

    Science.gov (United States)

    Helms, Mike W.; Prescher, Jennifer A.; Cao, Yu-An; Schaffert, Steven

    2016-01-01

    Cytokine-induced killer (CIK) cells are T cell derived ex vivo expanded cells with both NK and T cell properties. They exhibit potent anti-tumor efficacy against various malignancies in preclinical models and have proven safe and effective in clinical studies. We combined CIK cell adoptive immunotherapy with IL-12 cytokine immunotherapy in an immunocompetent preclinical breast cancer model. Combining CIK cells with IL-12 increased anti-tumor efficacy in vivo compared to either therapy alone. Combination led to full tumor remission and long-term protection in 75% of animals. IL-12 treatment sharply increased the anti-tumor efficacy of short-term cultured CIK cells that exhibited no therapeutic effect alone. Bioluminescence imaging based in vitro cytotoxicity and in vivo homing assays revealed that short-term cultured CIK cells exhibit full cytotoxicity in vitro, but display different tumor homing properties than fully expanded CIK cells in vivo. Our data suggest that short-term cultured CIK cells can be “educated” in vivo, producing fully expanded CIK cells upon IL-12 administration with anti-tumor efficacy in a mouse model. Our findings demonstrate the potential to improve current CIK cell-based immunotherapy by increasing efficacy and shortening ex vivo expansion time. This holds promise for a highly efficacious cancer therapy utilizing synergistic effects of cytokine and cellular immunotherapy. PMID:20532883

  18. Efficacy of liver parenchymal enhancement and liver volume to standard liver volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function

    Energy Technology Data Exchange (ETDEWEB)

    Yoneyama, Tomohide; Fukukura, Yoshihiko; Kamimura, Kiyohisa; Takumi, Koji; Umanodan, Aya; Nakajo, Masayuki [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Radiology, Kagoshima City (Japan); Ueno, Shinichi [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Surgical Oncology and Digestive Surgery, Kagoshima City (Japan)

    2014-04-15

    We aimed to develop and assess the efficacy of a liver function index that combines liver enhancement and liver volume to standard liver volume (LV/SLV) ratio on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. In all, 111 patients underwent a Gd-EOB-DTPA-enhanced MRI, including T1 mapping, before and 20 min after Gd-EOB-DTPA administration. We calculated the following Gd-EOB-DTPA-enhanced MRI-based liver function indices: relative enhancement of the liver, corrected enhancement of the liver-to-spleen ratio, LSC{sub N}20, increase rate of the liver-to-muscle ratio, reduction rate of T1 relaxation time of the liver, ΔR1 of the liver and K{sub Hep}; the indices were multiplied by the LV/SLV ratio. We calculated the correlations between an indocyanine green (ICG) clearance and the Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio, by using Pearson correlation analysis. There were significant correlations between all Gd-EOB-DTPA-enhanced MRI-based liver function indices and ICG clearance (r = -0.354 to -0.574, P < 0.001). All Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio (r = -0.394 to -0.700, P < 0.001) were more strongly correlated with the ICG clearance than those without multiplication by the LV/SLV ratio. Gd-EOB-DTPA-enhanced MRI-based liver function indices that combine liver enhancement and the LV/SLV ratio may more reliably estimate liver function. (orig.)

  19. Artemether-lumefantrine nanostructured lipid carriers for oral malaria therapy: Enhanced efficacy at reduced dose and dosing frequency.

    Science.gov (United States)

    Prabhu, Priyanka; Suryavanshi, Shital; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2016-09-10

    Artemether-lumefantrine (ARM-LFN) is a World Health Organization (WHO) approved fixed-dose combination having low solubility and poor oral bioavailability. Nanostructured lipid carriers (NLC) were developed to enhance the oral efficacy of this combination using the microemulsion template technique. They were characterized for drug content, entrapment efficiency, size distribution, in vitro release, antimalarial efficacy, and toxicity. The NLC showed sustained drug release. The recommended adult therapeutic dose is 80mg ARM and 480mg LFN (4 tablets) twice a day, which amounts to 160mg ARM and 960mg LFN daily. ARM-LFN NLC given once a day at 1/5 of therapeutic dose (16mg ARM and 96mg LFN) showed complete parasite clearance and 100% survival in Plasmodium berghei-infected mice. 33% of the mice treated with marketed tablets twice a day at the therapeutic dose showed late-stage recrudescence. Thus, NLC showed enhanced efficacy at 1/10 of the daily dose of ARM-LFN. The 10-fold reduced daily dose was formulated in two soft gelatin capsules thus reducing the number of units to be taken at a time by the patient. The capsules showed good stability at room temperature for a year. The NLC were found to be safe in rats. The biocompatible NLC developed using an industrially feasible technique offer a promising solution for oral malaria therapy. PMID:27421912

  20. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    International Nuclear Information System (INIS)

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression

  1. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  2. How Setting Goals Enhances Learners’ Self-Efficacy Beliefs in Listening Comprehension

    Directory of Open Access Journals (Sweden)

    Liliana Ballesteros Muñoz

    2014-04-01

    Full Text Available This article outlines a study that explores the relationship between SMART goal setting (Specific, Measurable, Attainable, Relevant, and Time-based and learning English in Colombia concerning a foreign language learners’ self-efficacy beliefs in listening. The participants were seventh and ninth grade students of two schools in Bogotá, Colombia. The results revealed that self-efficacy was highly positive when related to goal setting as students were able to set SMART goals to improve their listening comprehension and learners showed improvement in self-efficacy beliefs and felt more motivated while completing listening tasks related to songs. Furthermore this study shows that goal setting training can be incorporated successfully into the English as a foreign language classroom.

  3. Enhancing Self-Efficacy in Elementary Science Teaching with Professional Learning Communities

    Science.gov (United States)

    Mintzes, Joel J.; Marcum, Bev; Messerschmidt-Yates, Christl; Mark, Andrew

    2013-01-01

    Emerging from Bandura's Social Learning Theory, this study of in-service elementary school teachers examined the effects of sustained Professional Learning Communities (PLCs) on self-efficacy in science teaching. Based on mixed research methods, and a non-equivalent control group experimental design, the investigation explored changes in…

  4. Enhancing Students' Learning and Self- Efficacy through Blended Learning in a Teachers' Program

    Science.gov (United States)

    Abdelraheem, Ahmed Yousif

    2014-01-01

    Blended Learning (BL) strategies play an important role in collaboration, communication skills, motivation, attitudes, interaction with the subject and practical skills. However, their relationship with students' learning and self efficacy were not studied enough and this was the focus of this study. Therefore, the aim of the study was to…

  5. Enhanced Antitumor Efficacy and Reduced Toxicity of Docetaxel Loaded Estradiol Functionalized Stealth Polymeric Nanoparticles

    DEFF Research Database (Denmark)

    Jain, Sanyog; Spandana, Gollapalli; Agrawal, Ashish Kumar; Kushwah, Varun; Thanki, Kaushik

    2015-01-01

    antitumor efficacy in DMBA induced rat model demonstrated significant reduction in tumor volume in comparison with the plain counterpart (PLGA-NPs) and a marketed formulation, Taxotere. Moreover, the safety of the estradiol functionalized PLGA NPs was confirmed by hepato- and nephrotoxicity studies....

  6. Powerpoint's Power in the Classroom: Enhancing Students' Self-Efficacy and Attitudes

    Science.gov (United States)

    Susskind, J.E.

    2005-01-01

    The current study examined the effects of non-interactive computer assisted instruction on students' performance, self-efficacy, motivation, and attitudes. Half the lectures presented to two Introduction to Psychology college classes were taught in a traditional lecture format and half were accompanied by PowerPoint multimedia. Lecture order was…

  7. Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice.

    Science.gov (United States)

    Kim, Jae; John, Joel; Langford, Dianne; Walker, Ellen; Ward, Sara; Rawls, Scott M

    2016-03-01

    The β-lactam antibiotic ceftriaxone (CTX) reduces cocaine reinforcement and relapse in preclinical assays through a mechanism involving activation of glutamate transporter subtype 1 (GLT-1). However, its poor brain penetrability and intravenous administration route may limit its therapeutic utility for indications related to CNS diseases. An alternative is clavulanic acid (CA), a structural analog of CTX that retains the β-lactam core required for GLT-1 activity but displays enhanced brain penetrability and oral activity relative to CTX. Here, we tested the hypothesis that CA (1, 10 mg/kg ip) would enhance GLT-1 expression and decrease cocaine self-administration (SA) in mice, but at lower doses than CTX. Experiments revealed that GLT-1 transporter expression in the nucleus accumbens of mice treated with repeated CA (1, 10 mg/kg) was enhanced relative to saline-treated mice. Repeated CA treatment (1 mg/kg) reduced the reinforcing efficacy of cocaine (0.56 mg/kg/inf) in mice maintained on a progressive-ratio (PR) schedule of reinforcement but did not affect acquisition of cocaine SA under fixed-ratio responding or acquisition or retention of learning. These findings suggest that the β-lactamase inhibitor CA can activate the cellular glutamate reuptake system in the brain reward circuit and reduce cocaine's reinforcing efficacy at 100-fold lower doses than CTX. PMID:26543027

  8. Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model.

    Science.gov (United States)

    Ouyang, Mao; White, Ethan E; Ren, Hui; Guo, Qin; Zhang, Ian; Gao, Hang; Yanyan, Song; Chen, Xuebo; Weng, Yiming; Da Fonseca, Anna; Shah, Sunny; Manuel, Edwin R; Zhang, Leying; Vonderfecht, Steven L; Alizadeh, Darya; Berlin, Jacob M; Badie, Behnam

    2016-01-01

    Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs) can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261) tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc) that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG. PMID:26829221

  9. Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model.

    Directory of Open Access Journals (Sweden)

    Mao Ouyang

    Full Text Available Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261 tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG.

  10. Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against Streptococcus pneumoniae with Elevated Amoxicillin MICs and Haemophilus influenzae

    OpenAIRE

    Berry, Valerie; Hoover, Jennifer; Singley, Christine; Woodnutt, Gary

    2005-01-01

    A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate (2,000 mg of amoxicillin/125 mg of clavulanate twice a day; ratio 16:1) has been designed, with sustained-release technology, to allow coverage of bacterial strains with amoxicillin-clavulanic acid MICs of at least 4/2 μg/ml. The bacteriological efficacy of amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was compared in a rat model of respiratory tract infection versus four other amoxicillin-clavulanate f...

  11. Luminous efficacy enhancement of ultraviolet-excited white light-emitting diodes through multilayered phosphor-in-glass.

    Science.gov (United States)

    Peng, Yang; Wang, Sinmin; Li, Ruixin; Li, Hong; Cheng, Hao; Chen, Mingxiang; Liu, Sheng

    2016-06-20

    To enhance the luminous efficacy of ultraviolet-excited white light-emitting diodes (WLEDs), a novel packaging structure that is based on a multilayered red, green, and blue (RGB) phosphor-in-glass (PiG) was proposed. The RGB PiG was prepared by screenprinting and low temperature sintering, and the effects of different configuration orders of RGB phosphor layers on the optical performance of WLEDs were studied. Compared with the conventional mixed-RGB PiG, the luminous efficacy of WLEDs packaged by the multilayered PiG with the order of R-G-B is increased by 8.2% at the driving current of 500 mA, and the corresponding correlated color temperature (CCT) and color rendering index (CRI) are 2984 K and 86.8, respectively. Moreover, the WLEDs packaged by multilayered G-R-B PiG yield the highest luminous efficacy of 27.19 lm/W at the expense of color quality, which is still an acceptable warm light, with a CCT of 3326 K and a CRI of 84.2. PMID:27409121

  12. Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery.

    Science.gov (United States)

    Bandeira, Elga; Lopes-Pacheco, Miquéias; Chiaramoni, Nadia; Ferreira, Débora; Fernandez-Ruocco, Maria J; Prieto, Maria J; Maron-Gutierrez, Tatiana; Perrotta, Ramiro M; de Castro-Faria-Neto, Hugo C; Rocco, Patricia R M; Alonso, Silvia Del Valle; Morales, Marcelo M

    2016-01-01

    Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases. PMID:27199766

  13. Association with amino acids does not enhance efficacy of polymerized liposomes as a system for lung gene delivery

    Directory of Open Access Journals (Sweden)

    Elga eBernardo Bandeira De Melo

    2016-04-01

    Full Text Available Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids (1,2-bis-(tricosa-10,12-diynoyl-sn-glycero-3-phosphocholine associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with L-arginine, L-tryptophan, or L-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. L-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases.

  14. Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery

    Science.gov (United States)

    Bandeira, Elga; Lopes-Pacheco, Miquéias; Chiaramoni, Nadia; Ferreira, Débora; Fernandez-Ruocco, Maria J.; Prieto, Maria J.; Maron-Gutierrez, Tatiana; Perrotta, Ramiro M.; de Castro-Faria-Neto, Hugo C.; Rocco, Patricia R. M.; Alonso, Silvia del Valle; Morales, Marcelo M.

    2016-01-01

    Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases. PMID:27199766

  15. Inhibition of phosphoserine phosphatase enhances the anticancer efficacy of 5-fluorouracil in colorectal cancer.

    Science.gov (United States)

    Li, Xin; Xun, Zhe; Yang, Yong

    2016-09-01

    Most colorectal cancer (CRC) cell lines are identified to overexpress phosphoserine phosphatase (PSPH), which regulates the intracellular synthesis of serine and glycine, and supports tumor growth. In this study, the effect of PSPH on 5-fluorouracil (5-FU) efficacy was evaluated. CRC cells exposed to 5-FU acquire metabolic remodeling, resulting in increased glucose flux for PSPH-mediated serine synthesis. Then serine is converted into GSH, which promotes cell survival through the detoxification of 5-FU-induced reactive oxygen species (ROS). Consequently, repression of PSPH by the use of shRNAs for PSPH impaired the defense against drug-induced oxidative stress, thereby sensitizing cells to 5-FU. The importance of the PSPH in supporting tumor growth during 5-FU treatment was also demonstrated in an in vivo tumor model of CRC. These findings indicate that the PSPH could serve as a target for increasing the anticancer efficacy of conventional therapy in patients with CRC. PMID:27349874

  16. Enhancing role breadth self-efficacy: the roles of job enrichment and other organizational interventions.

    Science.gov (United States)

    Parker, S K

    1998-12-01

    Role breadth self-efficacy (RBSE) refers to employees' perceived capability of carrying out a broader and more proactive set of work tasks that extend beyond prescribed technical requirements. A newly developed scale of RBSE was internally consistent and distinct from the related concepts of proactive personality and self-esteem. In an initial cross-sectional study (N = 580), work design variables (job enrichment, job enlargement, and membership of improvement groups) were the key organizational predictors of RBSE. These investigations were repeated in a second cross-sectional study (N = 622) and extended by examining change over time (N = 459). The longitudinal analysis showed that increased job enrichment and increased quality of communication predicted the development of greater self-efficacy. PMID:9885197

  17. Digital Self-Efficacy and Language Learning Enhancement in an Online Setting

    OpenAIRE

    Shakarami, Alireza; Khajehei, H.; Hajhashemi, Karim

    2013-01-01

    The importance of personal factors such as personality traits, learning strategies, self-esteem, and self-efficacy in the complicated task of language learning has been established for years. However, the introduction of computers, networks and their wide communication affordances, seem to impact many aspects of learning and teaching and particularly language learning and teaching. The storage place, manner, and magnitude of learning materials for example, have shifted from the human mind to ...

  18. Efficacy of Carcass Electrical Stimulation in Meat Quality Enhancement: A Review

    OpenAIRE

    Adeyemi, Kazeem Dauda; Sazili, Awis Qurni

    2014-01-01

    The use of electrical stimulation (ES) as a management tool to improve meat quality and efficiency of meat processing is reviewed. The basis of the efficacy of ES is its ability to fast track postmortem glycolysis, which in turn stimulates myriad histological, physical, biochemical, biophysical and physiological changes in the postmortem muscle. Electrical stimulation hastens the onset and resolution of rigor mortis thereby reducing processing time and labor and plays a vital role in improvin...

  19. HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

    OpenAIRE

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

    2014-01-01

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral act...

  20. Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis.

    Science.gov (United States)

    Cirioni, Oscar; Simonetti, Oriana; Pierpaoli, Elisa; Barucca, Alessandra; Ghiselli, Roberto; Orlando, Fiorenza; Pelloni, Maria; Minardi, Daniele; Trombettoni, Maria Michela Cappelletti; Guerrieri, Mario; Offidani, Annamaria; Giacometti, Andrea; Provinciali, Mauro

    2016-08-01

    We investigated the efficacy of colistin combined with pexiganan in experimental mouse models of Acinetobacter baumannii infection.Adult male BALB/c mice received intraperitoneally 1 mL saline containing 2 × 10 CFU of susceptible and multiresistant A. baumannii. Two hours after bacterial challenge, animals received 1 mg/kg of colistin, 1 mg/kg of pexiganan, or 1 mg/kg of colistin plus 1 mg/kg of pexiganan.Blood culture positivity, the quantities of bacteria in the intra-abdominal fluid, the rate of lethality and immunological studies, such as immunophenotyping and NK cytotoxicity, were evaluated.In the in vitro study, A. baumannii showed susceptibility to colistin and pexiganan and a strong synergy was observed by testing colistin combined with pexiganan with fractionary inhibitory concentration index of 0.312 for both strains.In the in vivo study colistin or pexiganan alone showed a good antimicrobial efficacy. When colistin was combined with pexiganan, the positive interaction produced low bacterial counts that were statistically significant versus singly treated groups. For both strains the highest rate of survival was observed in combined-treated groups (90%).Pexiganan increased NK cytotoxic activity over the levels of infected and colistin-treated animals.In conclusion, pexiganan combined with colistin was found to be efficacious against A. baumannii infection. PMID:26849630

  1. Combined active and passive immunization enhances the efficacy of immunotherapy against nicotine in rats.

    Science.gov (United States)

    Roiko, Samuel A; Harris, Andrew C; Keyler, Daniel E; Lesage, Mark G; Zhang, Yan; Pentel, Paul R

    2008-06-01

    Vaccination against nicotine reduces the behavioral effects of nicotine in rats, and it is under clinical evaluation as a treatment for tobacco addiction. Efficacy is limited by the need for high serum nicotine-specific antibody (NicAb) levels, and currently available nicotine vaccines do not uniformly generate the required NicAb levels. Passive immunization with a nicotine-specific monoclonal antibody (Nic311) has also shown efficacy in rats. The principal aim of this study was to determine whether the combined use of vaccination and passive immunization would produce greater effects than vaccination alone on nicotine pharmacokinetics and locomotor sensitization (LMS) to nicotine. Rats were treated with vaccination alone, Nic311 alone, both, or neither, and then they were administered 10 daily injections of 0.3 mg/kg nicotine s.c. Treatment with Nic311 or vaccination alone increased the binding of nicotine in serum, reduced the unbound serum nicotine concentration and nicotine distribution to brain, and attenuated the development of LMS. Combined use of vaccination and passive immunization produced higher total serum NicAb levels, greater changes in nicotine pharmacokinetics, and a greater attenuation of LMS than either treatment alone. The total serum NicAb concentration was significantly correlated with brain nicotine levels and locomotor activity. These data indicate that providing higher serum NicAb concentrations improves the efficacy of immunotherapy against nicotine and that supplementing vaccination with passive immunization is a potential strategy to accomplish this. PMID:18305013

  2. Cystic echinococcosis therapy: Albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice.

    Science.gov (United States)

    Pensel, Patricia E; Ullio Gamboa, Gabriela; Fabbri, Julia; Ceballos, Laura; Sanchez Bruni, Sergio; Alvarez, Luis I; Allemandi, Daniel; Benoit, Jean Pierre; Palma, Santiago D; Elissondo, María C

    2015-12-01

    Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE. PMID:26409727

  3. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  4. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ.

    Science.gov (United States)

    Barkhouse, Darryll A; Faber, Milosz; Hooper, D Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. PMID:25463615

  5. RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer.

    Science.gov (United States)

    Wang, Fangfang; Chen, Lei; Zhang, Rui; Chen, Zhongping; Zhu, Li

    2014-12-28

    Targeting αvβ3 integrin is particularly promising for the treatment of bone metastases by targeting integrin-rich tumor cells and by inhibiting integrin-involved bone metastases. In this work, a liposomal drug delivery system conjugated with cyclic arginine-glycine-aspartic acid-tyrosine-lysine peptide (cRGDyk) as αvβ3 integrin ligand was thus developed to improve therapeutic efficacy in a mice model of bone metastasis from prostate cancer. The resultant liposomes were characterized in terms of size, morphology, zeta potential, stability, drug encapsulation percentage and loading efficiency, and drug release. Compared with free cisplatin and cRGDyk-free liposomes, cRGDyk conjugated liposomes showed significantly higher cellular uptake and higher cytotoxicity of loaded cisplatin, as evidenced by in vitro cell experiments. In vivo results revealed that free cisplatin and free cRGDyk could relieve tumor-induced pain but had no contributions to tumor regression and overall survival improvement. cRGDyk-free liposomal drug system with prolonged blood circulation time could accumulated in the tumor sites in the bone through enhanced permeability and retention (EPR) effects and however, did not exhibit desirable therapeutic efficacy superior to free cisplatin and free cRGDyk. This strongly suggested that ERP effects were not effective in treating metastases. By taking advantages of targeted drug delivery and synergistic antitumor activity of cRGDyk and loaded cisplatin, cRGDyk conjugated liposomal drug system could inhibit osteoclastic and osteoblastic bone lesions, relieve pain, and improve overall survival. Inspired by their enhanced therapeutic efficacy and low organ toxicity, cRGDyk conjugated liposomes could serve as an effective drug system for targeted and synergistic therapy of bone metastases. PMID:25456829

  6. Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2

    OpenAIRE

    Pearson, Mark S.; Pickering, Darren A.; McSorley, Henry J.; Bethony, Jeffrey M; Tribolet, Leon; Dougall, Annette M.; Hotez, Peter J.; Loukas, Alex

    2012-01-01

    The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubilit...

  7. NOVEL DELIVERY SYSTEM ENHANCES EFFICACY OF ANTIRETROVIRAL THERAPY IN ANIMAL MODEL FOR HIV-1 ENCEPHALITIS (HIVE)

    OpenAIRE

    Spitzenberger, Timothy J.; Heilman, David; Diekmann, Casey; Batrakova, Elena; Kabanov, Alexander; Gendelman, Howard E.; Elmquist, William F.; Persidsky, Yuri

    2006-01-01

    Most potent anti-retroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of anti-retroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). SCID mice inoculated with HIV-1 infected human monocyt...

  8. Investigation of the Efficacy of Transdermal Penetration Enhancers Through the Use of Human Skin and a Skin Mimic Artificial Membrane.

    Science.gov (United States)

    Balázs, Boglárka; Vizserálek, Gábor; Berkó, Szilvia; Budai-Szűcs, Mária; Kelemen, András; Sinkó, Bálint; Takács-Novák, Krisztina; Szabó-Révész, Piroska; Csányi, Erzsébet

    2016-03-01

    The aim of this study was to investigate the behavior of promising penetration enhancers through the use of 2 different skin test systems. Hydrogel-based transdermal formulations were developed with ibuprofen as a nonsteroidal anti-inflammatory drug. Transcutol and sucrose esters were used as biocompatible penetration enhancers. The permeability measurements were performed with ex vivo Franz diffusion cell methods and a newly developed Skin Parallel Artificial Membrane Permeability Assays (PAMPA) model. Franz diffusion measurement is commonly used as a research tool in studies of diffusion through synthetic membranes in vitro or penetration through ex vivo human skin, whereas Skin PAMPA involves recently published artificial membrane-based technology for the fast prediction of skin penetration. It is a 96-well plate-based model with optimized artificial membrane structure containing free fatty acid, cholesterol, and synthetic ceramide analog compounds to mimic the stratum corneum barrier function. Transdermal preparations containing 2.64% of different sucrose esters and/or Transcutol and a constant (5%) of ibuprofen were investigated to determine the effects of these penetration enhancers. The study demonstrated the good correlation of the permeability data obtained through use of human skin membrane and the in vitro Skin PAMPA system. The Skin PAMPA artificial membrane serves as quick and relatively deep tool in the early stages of transdermal delivery systems, through which the enhancing efficacy of excipients can be screened so as to facilitate the choice of effective penetration components. PMID:26886318

  9. Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth

    OpenAIRE

    Shishido, Stephanie N.; Nguyen, Thu A.

    2012-01-01

    Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs) acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increa...

  10. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.

    Science.gov (United States)

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  11. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Science.gov (United States)

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  12. Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

    Directory of Open Access Journals (Sweden)

    Youngsoo Sohn

    2013-03-01

    Full Text Available Human α-galactosidase A (GLA has been used in enzymereplacement therapy for patients with Fabry disease. Weexpressed recombinant GLA from Chinese hamster ovary cellswith very high productivity. When compared to an approvedGLA (agalsidase beta, its size and charge were found to besmaller and more neutral. These differences resulted from thelack of terminal sialic acids playing essential roles in the serumhalf-life and proper tissue targeting. Because a simplesialylation reaction was not enough to increase the sialic acidcontent, a combined reaction using galactosyltransferase,sialyltransferase, and their sugar substrates at the same timewas developed and optimized to reduce the incubation time.The product generated by this reaction had nearly the samesize, isoelectric points, and sialic acid content as agalsidasebeta. Furthermore, it had better in vivo efficacy to degrade theaccumulated globotriaosylceramide in target organs of Fabrymice compared to an unmodified version. [BMB Reports 2013;46(3: 157-162

  13. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  14. Pre-flight Functionality Check to Enhance Mission Efficacy of Precision Guided Munitions

    Directory of Open Access Journals (Sweden)

    A. K. Maini

    2009-09-01

    Full Text Available Precision-guided munitions (PGMs, because of their precision strike capability, are used extensively in the modern warfare. The efficacy of the mission is critically dependent on the successful deployment of the weapon. To ensure high level of effectiveness of these sophisticated weapons, these must be tested at regular intervals. Periodic functionality checks of these weapons are carried out using comprehensive characterisation systems. In addition to comprehensive testing, pre-flight functionality checks with the weapon strapped on to the launchplatform using portable test systems should be carried out. These functionality checks, also referred to as serviceability checks, perform Go/No Go testing of the weapon by focusing on one or two vital parameters of the guided weapon. Pre-flight functionality check of PGM allows a quick appraisal on the functional status of the vital operational parameters of relevance to efficacy of the mission. This review highlights the parameters that need to be checked, both for comprehensive testing of these weapons on a periodic basis and also those required for pre-flight functionality or readiness checks. International systems available for the purpose have also been reviewed, vis-à-vis, their capabilities and limitations to perform the two types of tests with particular emphasis on the pre-flight functionality checks with guided weapon in strap-on condition. Some alternative design approaches have also been proposed.Defence Science Journal, 2009, 59(5, pp.459-465, DOI:http://dx.doi.org/10.14429/dsj.59.1547

  15. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Kocdor H

    2015-07-01

    Full Text Available Hilal Kocdor,1,2 Halil Ates,1 Suleyman Aydin,3 Ruksan Cehreli,1 Firat Soyarat,2 Pinar Kemanli,2 Duygu Harmanci,2 Hakan Cengiz,2 Mehmet Ali Kocdor4 1Institute of Oncology, Dokuz Eylul University, 2Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir Turkey; 3Department of Biochemistry, Firat University School of Medicine, Elazig, 4Department of Surgery, School of Medicine, Dokuz Eylul University, Izmir, Turkey Background: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.Methods: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549 and p53-null (H1299 cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.Results: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50 values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 µM and 100 µM.Conclusion: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells. Keywords: lung cancer, zinc, docetaxel, A549, H1299

  16. Newcastle disease virus chimeras expressing the Hemagglutinin- Neuraminidase protein of mesogenic strain exhibits an enhanced anti-hepatoma efficacy.

    Science.gov (United States)

    He, Jinjiao; Pan, Ziye; Tian, Guiyou; Liu, Xin; Liu, Yunye; Guo, Xiaochen; An, Ying; Song, Liying; Wu, Hongsong; Cao, Hongwei; Yu, Dan; Che, Ruixiang; Xu, Pengfei; Rasoul, Lubna M; Li, Deshan; Yin, Jiechao

    2016-08-01

    Newcastle disease virus (NDV) is an intrinsically tumor-specific virus, many researchers have reported that lentogenic NDV is a safe and effective agent for human cancer therapy. It had been demonstrated that the amino acid sequence of the fusion protein cleavage site is a major factor in the pathogenicity and anti-tumor efficacy of rNDV. However, the role of Hemagglutinin-Neuraminidase (HN) gene that contributes to virulence and anti-tumor efficacy remains undefined. To assess the role of HN gene in virus pathogenicity and anti-tumor efficacy, a reverse genetic system was developed using the lentogenic NDV Clone30 strain to provide backbone for gene exchange. Chimeric virus (rClone30-Anh(HN)) created by exchange of the HN gene of lentogenic strain Clone30 with HN gene of mesogenic strain produce no significant changes in virus pathogenicity as assessed by conducting the mean death time (MDT) and intracerebral pathogenicity index (ICPI) assays. In vitro, infection with chimeras could induce the formation of syncytium relative significantly in HepG2 cells. Furthermore, chimeras was shown to induce the cell apoptosis via MTT and Annexin V-PI assays, reduce mitochondrial membrane potential and increase the mRNA transcription level of caspase 3. In vivo, ICR mice carrying tumor of hepatoma H22 cells were treated via intratumoral injection of chimeric virus. The treatment of chimera shows an obvious suppression in tumor volume. These results suggest that it could be an ideal approach to enhance the antitumor ability of Newcastle disease virus and highlighted the potential therapeutic application of rClone30-Anh(HN) as a viral vector to deliver foreign genes for treatment of cancers. PMID:27164362

  17. Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

    Science.gov (United States)

    Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

    2016-07-01

    The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. PMID:27063964

  18. From Burdens to Benefits: The Societal Impact of PDL-Enriched, Efficacy-Enhanced Educators

    Science.gov (United States)

    Shaha, Steven H.; Glassett, Kelly F.; Rosenlund, David; Copas, Aimee; Huddleston, T. Lisa

    2016-01-01

    Societies continue to absorb increased burdens in cost for helping citizens unable to achieve at optimal levels. Building on past research, we project educational benefits to offset current societal burdens through enhanced educator capabilities. Studies reviewed show participation in a high-impact professional development and learning solution…

  19. Investing in Administrator Efficacy: An Examination of Professional Development as a Tool for Enhancing Principal Effectiveness

    Science.gov (United States)

    Grissom, Jason A.; Harrington, James R.

    2010-01-01

    A primary goal of school districts' investments in professional development for principals is to enhance their effectiveness. This study examines the connection between administrator professional development and performance in a national sample of schools. We show that not all types of administrator professional development participation correlate…

  20. Interaction of pre- and post-emergence herbicide treatment on efficacy of different black-grass biotypes with enhanced metabolism

    Directory of Open Access Journals (Sweden)

    Petersen, Jan

    2014-02-01

    Full Text Available In an outdoor container trial with different resistant black-grass biotypes with enhanced metabolism, efficacy of pre- and post-emergence treatments as well as their sequence was investigated in spring wheat. Weed control success was compared to a susceptible biotype. Results indicate that there are strong interactions between herbicide and black-grass biotypes. As a consequence site specific herbicide strategies corresponding to current herbicide resistance situation can be necessary. If further trials support these findings than it is essential to characterize the site specific herbicide resistance situation and the potential interactions between different biotypes x herbicides resp. sequences. Only under these circumstances it is possible to optimize the herbicide choice on a specific site. Black-grass control might be optimal than and further speed of resistance evolution might be reduced on that site.

  1. [Evaluating the efficacy of a program to enhance college students' self-regulation learning processes and learning strategies].

    Science.gov (United States)

    Rosário, Pedro; Mourao, Rosa; Núñez, José C; González-Pienda, Julio; Solano, Paula; Valle, Antonio

    2007-08-01

    The present study examines the efficacy of a program designed to enhance college students'learning processes and study strategies. The program was organised around a number of letters written by a freshman, Gervásio (Rosário, Núñez, & González-Pienda, 2006), telling about his new experiences, troubles, and successes in the university. This intervention program is intended to promote a series of strategies (cognitive, meta-cognitive, and supportive) which allow students to manage their learning processes in a more proficient, successful, and autonomous way. The collected data suggest that students who had the opportunity to follow the program significantly improved their declarative knowledge about learning strategies, reduced their use of surface approaches to study, and extended the newly acquired skills to new and different tasks and assignments. PMID:17617980

  2. Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi.

    Science.gov (United States)

    Bah, Germanus S; Tanya, Vincent N; Makepeace, Benjamin L

    2015-08-15

    Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, has been successfully controlled by a single drug, ivermectin, for over 25 years. Ivermectin prevents the disease symptoms of severe itching and visual impairment by killing the microfilarial stage, but does not eliminate the adult parasites, necessitating repeated annual treatments. Mass drug administration with ivermectin does not always break transmission in forest zones and is contraindicated in individuals heavily co-infected with Loa loa, while reports of reduced drug efficacy in Ghana and Cameroon may signal the development of resistance. An alternative treatment for onchocerciasis involves targeting the essential Wolbachia symbiont with tetracycline or its derivatives, which are adulticidal. However, implementation of antibiotic therapy has not occurred on a wide scale due to the prolonged treatment regimen required (several weeks). In the bovine Onchocerca ochengi system, it has been shown previously that prolonged oxytetracycline therapy increases eosinophil counts in intradermal nodules, which kill the adult worms by degranulating on their surface. Here, in an "immunochemotherapeutic" approach, we sought to enhance the efficacy of a short, sub-lethal antibiotic regimen against O. ochengi by prior immunotherapy targeting onchocystatin, an immunomodulatory protein located in the adult female worm cuticle. A key asparagine residue in onchocystatin was mutated to ablate immunomodulatory activity, which has been demonstrated previously to markedly improve the protective efficacy of this vaccine candidate when used as an immunoprophylactic. The immunochemotherapeutic regimen was compared with sub-lethal oxytetracycline therapy alone; onchocystatin immunotherapy alone; a gold-standard prolonged, intermittent oxytetracycline regimen; and no treatment (negative control) in naturally infected Cameroonian cattle. Readouts were collected over one year and comprised adult

  3. Electrolytic Generation of Oxygen Partially Explains Electrical Enhancement of Tobramycin Efficacy against Pseudomonas aeruginosa Biofilm

    OpenAIRE

    Stewart, Philip S.; Wattanakaroon, Wanida; Goodrum, Lu; Fortun, Susana M.; McLeod, Bruce R.

    1999-01-01

    The role of electrolysis products, including protons, hydroxyl ions, reactive oxygen intermediates, oxygen, hydrogen, and heat, in mediating electrical enhancement of killing of Pseudomonas aeruginosa biofilms by tobramycin (the bioelectric effect) was investigated. The log reduction in biofilm viable cell numbers compared to the numbers for the untreated positive control effected by antibiotic increased from 2.88 in the absence of electric current to 5.58 in the presence of electric current....

  4. Engineering of Hollow Mesoporous Silica Nanoparticles for Remarkably Enhanced Tumor Active Targeting Efficacy

    OpenAIRE

    Chen, Feng; Hong, Hao; Shi, Sixiang; Goel, Shreya; Valdovinos, Hector F.; Hernandez, Reinier; Theuer, Charles P.; Barnhart, Todd E.; Cai, Weibo

    2014-01-01

    Hollow mesoporous silica nanoparticle (HMSN) has recently gained increasing interests due to their tremendous potential as an attractive nano-platform for cancer imaging and therapy. However, possibly due to the lack of efficient in vivo targeting strategy and well-developed surface engineering techniques, engineering of HMSN for in vivo active tumor targeting, quantitative tumor uptake assessment, multimodality imaging, biodistribution and enhanced drug delivery have not been achieved to dat...

  5. Enhancing self-efficacy to enable entrepreneurship: The case of CMI€ٳ Connections

    OpenAIRE

    Lucas, William A.; Cooper, Sarah Y.

    2005-01-01

    Enhancing levels of innovation and entrepreneurship to grow a more competitive economy is the focus of much government effort. Attention is paid to changing a culture seen as antagonistic to entrepreneurship through initiatives designed to promote an entrepreneurial spirit. Universities, aware of the importance of developing entrepreneurial potential, are focusing on equipping students with the skills and abilities to contribute to innovation within organisations they join upon graduation, wh...

  6. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    OpenAIRE

    Kim Sung-Ho; Jung Uhee; Jo Sung-Kee; Ju Eun-Jin; Park Hae-Ran; Yee Sung-Tae

    2009-01-01

    Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of ...

  7. Advances in spinal cord stimulation - enhancement of efficacy, improved surgical technique and a new indication

    OpenAIRE

    Lind, Göran

    2012-01-01

    Introduction and aim: Spinal cord stimulation (SCS) has been used for treatment of otherwise therapy-resistant chronic neuropathic pain for about four decades. However, 30-40 % of the patients do not benefit from SCS, despite careful case selection and technical advances. In search of ways to improve the outcome mechanisms underlying the pain relieving effect of SCS have been extensively explored. Experimental findings suggest a possibility to enhance the effect of SCS by conco...

  8. Efficacy of Carcass Electrical Stimulation in Meat Quality Enhancement: A Review

    Science.gov (United States)

    Adeyemi, Kazeem Dauda; Sazili, Awis Qurni

    2014-01-01

    The use of electrical stimulation (ES) as a management tool to improve meat quality and efficiency of meat processing is reviewed. The basis of the efficacy of ES is its ability to fast track postmortem glycolysis, which in turn stimulates myriad histological, physical, biochemical, biophysical and physiological changes in the postmortem muscle. Electrical stimulation hastens the onset and resolution of rigor mortis thereby reducing processing time and labor and plays a vital role in improving meat tenderness and other meat quality traits. However, ES may have negative impacts on some meat quality traits such as color stability and water holding capacity in some animals. Electrical stimulation is not an end in itself. In order to achieve the desired benefits from its application, the technique must be properly used in conjunction with various intricate antemortem, perimortem and postmortem management practices. Despite extensive research on ES, the fundamental mechanisms and the appropriate commercial applications remained obscured. In addition, muscles differ in their response to ES. Thus, elementary knowledge of the various alterations with respect to muscle type is needed in order to optimize the effectiveness of ES in the improvement of meat quality. PMID:25049973

  9. Efficacy and Effectiveness of Physical Therapy in Enhancing Postural Control in Children With Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Susan R. Harris

    2005-01-01

    Full Text Available The purpose of this article was to conduct a systematic review of studies that examined the efficacy and effectiveness of postural control intervention strategies for children with CP. Only physical therapy interventions were included, e.g. adaptive seating devices, ankle foot orthoses, neurodevelopmental treatment. A multifaceted search strategy was employed to identify all potential studies published between 1990 and 2004. The search strategy included electronic databases, reference list scanning, author and citation tracking of relevant studies, and hand searching of pediatric physical therapy journals and conference proceedings. Twelve studies (1991–2004, comprising ten group design studies and two single subject studies, met our inclusion criteria. A variety of age ranges and severity of children with cerebral palsy (n = 132 participated in the studies. The study quality scores ranged from 2 to 7 (total possible range of 0 to 7 with a median score of 5.5 and a mode of 6. As was true in an earlier systematic review on adaptive seating, most of the 12 ‘experimental’ studies published since 1990 that were aimed at evaluating the effectiveness of postural control strategies provided lower levels of evidence, i.e. Sackett Levels III to V. Additional studies with stronger designs are needed to establish that postural control interventions for children with CP are effective.

  10. Berberine Nanosuspension Enhances Hypoglycemic Efficacy on Streptozotocin Induced Diabetic C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Zhiping Wang

    2015-01-01

    Full Text Available Berberine (Ber, an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg. These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.

  11. A Non-invasive Real-time Localization System for Enhanced Efficacy in Nasogastric Intubation.

    Science.gov (United States)

    Sun, Zhenglong; Foong, Shaohui; Maréchal, Luc; Tan, U-Xuan; Teo, Tee Hui; Shabbir, Asim

    2015-12-01

    Nasogastric (NG) intubation is one of the most commonly performed clinical procedures. Real-time localization and tracking of the NG tube passage at the larynx region into the esophagus is crucial for safety, but is lacking in current practice. In this paper, we present the design, analysis and evaluation of a non-invasive real-time localization system using passive magnetic tracking techniques to improve efficacy of the clinical NG intubation process. By embedding a small permanent magnet at the insertion tip of the NG tube, a wearable system containing embedded sensors around the neck can determine the absolute position of the NG tube inside the body in real-time to assist in insertion. In order to validate the feasibility of the proposed system in detecting erroneous tube placement, typical reference intubation trajectories are first analyzed using anatomically correct models and localization accuracy of the system are evaluated using a precise robotic platform. It is found that the root-mean-squared tracking accuracy is within 5.3 mm for both the esophagus and trachea intubation pathways. Experiments were also designed and performed to demonstrate that the system is capable of tracking the NG tube accurately in biological environments even in presence of stationary ferromagnetic objects (such as clinical instruments). With minimal physical modification to the NG tube and clinical process, this system allows accurate and efficient localization and confirmation of correct NG tube placement without supplemental radiographic methods which is considered the current clinical standard. PMID:26108204

  12. Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    Highlights: • Glycidyl nitrate (GLYN) is a NO generating small molecule and has ability to release NO on bioactivation in tumor cells. • GLYN-induced intracellular NO generation was attenuated by NO scavengers. • GLYN increases tumor blood flow in tumor-bearing animal model. • GLYN significantly increased the anti-tumor efficacy of cisplatin and radiation therapy in mice. • GLYN is well tolerated with no obvious systemic toxicities at its effective therapeutic doses in preclinical animal studies. - Abstract: Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds

  13. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

    Directory of Open Access Journals (Sweden)

    Citro Gennaro

    2008-11-01

    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  14. Diagnostic efficacy of gadoxetic acid-enhanced MRI for hepatocellular carcinoma and dysplastic nodule

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Saito; Fuminori Moriyasu; Katsutoshi Sugimoto; Ryota Nishio; Toru Saguchi; Toshitaka Nagao; Junichi Taira; Soichi oichi Akata; Koichi Tokuuye

    2011-01-01

    AIM: To evaluate the relationship between the signal intensity of hepatobiliary phase images on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and histological grade.METHODS: Fifty-nine patients with 82 hepatocellular lesions were evaluated retrospectively. Hepatobiliary phase images on gadoxetic acid-enhanced MRI were classified into 3 groups: low, iso or high. Angiography-assisted computed tomography (CT) findings were also classified into 3 groups: CT during arterial portography, and CT hepatic arteriography: A: iso, iso or low; B: slightly low, iso or low; and C: low, high. We correlated angiography-assisted CT, hepatobiliary phase findings during gadoxetic acid-enhanced MRI and histological grades. Furthermore, correlations between MRI findings and histological grade for each hemodynamic pattern were performed. Correlations among radiologicaland pathological findings were statistically evaluated using the chi-square test and Fisher' s exact test.RESULTS: There was a significant correlation between histological grade and hemodynamic pattern (P 0.05).CONCLUSION: Signal intensity in the hepatobiliary phase correlated with histological grade in the lesions that maintained portal blood flow, but did not correlate in lesions that showed decreased or defective portal blood flow.

  15. Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles

    Science.gov (United States)

    Mas, Núria; Galiana, Irene; Hurtado, Silvia; Mondragón, Laura; Bernardos, Andrea; Sancenón, Félix; Marcos, María D; Amorós, Pedro; Abril-Utrillas, Nuria; Martínez-Máñez, Ramón; Murguía, José Ramón

    2014-01-01

    pH-sensitive gated mesoporous silica nanoparticles have been synthesized. Increased extracellular pH and internalization into living yeast cells triggered molecular gate aperture and cargo release. Proper performance of the system was demonstrated with nanodevices loaded with fluorescein or with the antifungal agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole significantly enhanced tebuconazole cytotoxicity. As alterations of acidic external pH are a key parameter in the onset of fungal vaginitis, this nanodevice could improve the treatment for vaginal mycoses. PMID:24920897

  16. Blockade of PD-L1 Enhances the Therapeutic Efficacy of Combination Immunotherapy Against Melanoma1

    OpenAIRE

    Pilon-Thomas, Shari; Mackay, Amy; Vohra, Nasreen; Mulé, James J

    2010-01-01

    Inhibition of anti-tumor T cell responses can be mediated by the productive interaction between the programmed death-1 (PD-1) receptor on T cells and its ligand PD-L1. PD-L1 is highly expressed on both murine bone marrow-derived dendritic cells (DC) and B16 melanoma. In this study, in vitro blockade of PD-L1 interaction on DC led to enhanced IFN-gamma production and cytotoxicity by antigen-specific T cells. In vivo, the systemic administration of anti-PD-L1 antibody plus melanoma peptide-puls...

  17. Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery.

    Science.gov (United States)

    Rauta, Pradipta Ranjan; Das, Niladri Mohan; Nayak, Debasis; Ashe, Sarbani; Nayak, Bismita

    2016-08-01

    Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies. PMID:27463797

  18. Investigation of transfection efficacy with transcatheter arterial transporting transferring to enhance p53 gene

    International Nuclear Information System (INIS)

    Objective: To investigate the function of transferrin-DNA complex, transported by transferrin(Tf) and trans-arterial injection via interventional approach be the duel-target-orientated delivery and the transferring into malignant cells to get more effective therapy. Methods: p53-LipofectAMINE ligand with different concentrations of Tf (0, 10, 25, 50, 100 μg)transfected the 4 strains including LM6,Hep3B,YY and L02 in vitro to evaluate the gene transfection efficiency through western blot. Then, after setting up the VX2 hepatocarcinoma models, we delivered the Tf-p53-LipofectAMlNE complex into the hepatic arteries via interventional techniques to analyse the transfection efficiency in vivo. Results: Tf, within the range of l0 100 μg, could increase gene transfection efficiency mediated by liposome, and the efficiency increases with the raise of Tf concentration. Combination with interventional technique to inject Tf-DNA complex into tumor arteries, gene transfection efficiency was enhanced in rabbit models. Conclusion: Tf can enhance gene-liposome transfection efficiency, furthermore with combination of interventional catheter technique, there would be a potential duel-target-orientated gene therapy method. (authors)

  19. STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell.

    Science.gov (United States)

    Bu, Lin-Lin; Zhao, Zhi-Li; Liu, Jian-Feng; Ma, Si-Rui; Huang, Cong-Fa; Liu, Bing; Zhang, Wen-Feng; Sun, Zhi-Jun

    2015-12-01

    Signaling transducer and activator 3 (STAT3) and cancer stem cells (CSCs) have garnered huge attention as a therapeutic focus, based on evidence that they may represent an etiologic root of tumor initiation and radio-chemoresistance. Here, we investigated the high phosphorylation status of STAT3 (p-STAT3) and its correlation with self-renewal markers in head neck squamous cell carcinoma (HNSCC). Over-expression of p-STAT3 was found to have increased in post chemotherapy HNSCC tissue. We showed that blockade of p-STAT3 eliminated both bulk tumor and side population (SP) cells with characteristics of CSCs in vitro. Inhibition of p-STAT3 using small molecule S3I-201 significantly delayed tumorigenesis of spontaneous HNSCC in mice. Combining blockade of p-STAT3 with cytotoxic drugs cisplatin, docetaxel, 5-fluorouracil (TPF) enhanced the antitumor effect in vitro and in vivo with decreased tumor sphere formation and SP cells. Taken together, our results advocate blockade of p-STAT3 in combination with conventional chemotherapeutic drugs enhance efficacy by improving CSCs eradication in HNSCC. PMID:26556875

  20. Paclitaxel enhances therapeutic efficacy of the F8-IL2 immunocytokine to EDA-fibronectin-positive metastatic human melanoma xenografts.

    Science.gov (United States)

    Moschetta, Michele; Pretto, Francesca; Berndt, Alexander; Galler, Kerstin; Richter, Petra; Bassi, Andrea; Oliva, Paolo; Micotti, Edoardo; Valbusa, Giovanni; Schwager, Kathrin; Kaspar, Manuela; Trachsel, Eveline; Kosmehl, Hartwig; Bani, Maria Rosa; Neri, Dario; Giavazzi, Raffaella

    2012-04-01

    The selective delivery of bioactive agents to tumors reduces toxicity and enhances the efficacy of anticancer therapies. In this study, we show that the antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn), when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of EDA-Fn-expressing melanomas in combination with paclitaxel. We obtained curative effects with paclitaxel administered before the immunocytokine. Coadministration of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8-IL2-induced natural killer (NK) cells to the tumor, suggesting a host response as part of the observed therapeutic benefit. In support of this likelihood, NK cell depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly, this combination reduced both the tumor burden and the number of pulmonary metastatic nodules. The combination did not cause cumulative toxicity. Together, our findings offer a preclinical proof that by acting on the tumor stroma paclitaxel potentiates the antitumor activity elicited by a targeted delivery of IL2, thereby supporting the use of immunochemotherapy in the treatment of metastatic melanoma. PMID:22392081

  1. A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93.

    Directory of Open Access Journals (Sweden)

    Mark T Orr

    Full Text Available With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4(+ T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG.

  2. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Directory of Open Access Journals (Sweden)

    Wu SK

    2014-09-01

    Full Text Available Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 4Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan Abstract: The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The

  3. Efficacy of transvaginal contrast-enhanced MRI in the early staging of cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Akata, Deniz; Kerimoglu, Ulku; Hazirolan, Tuncay; Karcaaltincaba, Musturay; Oezmen, Mustafa N.; Akhan, Okan [Hacettepe University School of Medicine, Department of Radiology, Ankara (Turkey); Koese, Faruk [Social Security Hospital, Department of Gynecology, Ankara (Turkey)

    2005-08-01

    The objective of this study was to evaluate the efficacy of transvaginal contrast for local staging of cervical carcinoma. Fifty patients diagnosed with cervical carcinoma prospectively underwent magnetic resonance (MR) imaging before and after vaginal opacification (VO) with a mixture of 25 ml saline and 25 ml barium. T2-weighted (T2W) TSE images in axial and sagittal planes were compared before and after vaginal opacification. Dynamic T1W images in sagittal and fat-suppressed T1W images in transverse planes were also evaluated after intravenous contrast administration. Involvement of vaginal wall, lumen, and fornices; parametrium; rectum; and bladder were noted. Changes in local tumor staging and in treatment planning were also assessed after vaginal opacification. MR results were later compared with surgical pathological findings. Twenty-eight patients who went through surgical staging were included in the study. VO did not change any of the MR interpretations in 14 patients (50%). Correct staging was achieved with T2W TSE images with and without VO (in sagittal and transverse planes) in 78.5% and 50% of the patients, respectively. VO correctly lowered staging in seven and increased it in three patients compared with sagittal standard T2W images. Treatment planning was also changed in four (14%) of these patients. When overall accuracy of MR staging to indicate the appropriate treatment was evaluated, patients would have received the proper treatment in 90% and 79% of the cases when only T2W sagittal images with and without VO were evaluated, respectively. Dynamic gradient-echo images in sagittal planes and postcontrast T1W images in transverse planes evaluated with T2W series after VO, accomplished correct staging in 23 (82%) of the patients. MRI staging in early cervical cancer may be difficult and overestimated, especially if the tumor is slightly extended into the proximal vagina. Use of vaginal contrast medium is an easy, well-tolerated, and effective

  4. Use of biotin targeted methotrexate–human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy

    Directory of Open Access Journals (Sweden)

    Taheri A

    2011-09-01

    Full Text Available Azade Taheri1, Rassoul Dinarvand1,2, Faranak Salman Nouri1, Mohammad Reza Khorramizadeh3, Atefeh Taheri Borougeni4, Pooria Mansoori5, Fatemeh Atyabi1,21Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical sciences, Tehran, Iran; 3Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Tehran University of Medical Sciences, Tehran, Iran; 5Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranAbstract: Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA as a carrier. Methotrexate (MTX molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8% 21 days after treatment, whereas non-targeted MTX

  5. Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer

    Directory of Open Access Journals (Sweden)

    Li X

    2012-10-01

    Full Text Available Xiaolin Li,1,* Hua’e Xu,2,* Xinzheng Dai,3,4,* Zhenshu Zhu,5 Baorui Liu,6 Xiaowei Lu11Department of Geriatrics, 2Department of Pharmacy, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 3Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, 4Liver Transplantation Center, the First Affiliated Hospital to Nanjing Medical University, Nanjing; 5Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing; 6The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, China*These authors contributed equally to this workAbstract: Paclitaxel (Ptx, one of the most widely used anticancer agents, has demonstrated extraordinary activities against a variety of solid tumors. However, the therapeutic response of Ptx is often associated with severe side effects caused by its nonspecific cytotoxic effects and special solvents (Cremophor EL®. The current study reports the stable controlled release of Ptx/tetrandrine (Tet-coloaded nanoparticles by amphilic methoxy poly(ethylene glycol–poly(caprolactone block copolymers. There were three significant findings. Firstly, Tet could effectively stabilize Ptx-loaded nanoparticles with the coencapsulation of Tet and Ptx. The influence of different Ptx/Tet feeding ratios on the size and loading efficiency of the nanoparticles was also explored. Secondly, the encapsulation of Tet and Ptx into nanoparticles retains the synergistic anticancer efficiency of Tet and Ptx against mice hepatoma H22 cells. Thirdly, in the in vivo evaluation, intratumoral administration was adopted to increase the site-specific delivery. Ptx/Tet nanoparticles, when delivered intratumorally, exhibited significantly improved antitumor efficacy; moreover, they substantially increased the overall survival in an established H22-transplanted mice model. Further investigation into the

  6. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

    2008-06-02

    {beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

  7. Dual actions of albumin packaging and tumor targeting enhance the antitumor efficacy and reduce the cardiotoxicity of doxorubicin in vivo

    Directory of Open Access Journals (Sweden)

    Zheng K

    2015-08-01

    Full Text Available Ke Zheng,1 Rui Li,2 Xiaolei Zhou,2 Ping Hu,2 Yaxin Zhang,2 Yunmei Huang,3 Zhuo Chen,2 Mingdong Huang2 1College of Chemistry, Fuzhou University, Fuzhou, People’s Republic of China; 2State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, People’s Republic of China; 3Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Abstract: Doxorubicin (DOX is an effective chemotherapy drug used to treat different types of cancers. However, DOX has severe side effects, especially life-threatening cardiotoxicity. We herein report a new approach to reduce the toxicity of DOX by embedding DOX inside human serum albumin (HSA. HSA is further fused by a molecular biology technique with a tumor-targeting agent, amino-terminal fragment of urokinase (ATF. ATF binds with a high affinity to urokinase receptor, which is a cell-surface receptor overexpressed in many types of tumors. The as-prepared macromolecule complex (ATF–HSA:DOX was not as cytotoxic as free DOX to cells in vitro, and was mainly localized in cell cytosol in contrast to DOX that was localized in cell nuclei. However, in tumor-bearing mice, ATF–HSA:DOX was demonstrated to have an enhanced tumor-targeting and antitumor efficacy compared with free DOX. More importantly, histopathological examinations of the hearts from the mice treated with ATF–HSA:DOX showed a significantly reduced cardiotoxicity compared with hearts from mice treated with free DOX. These results demonstrate the feasibility of this approach in reducing the cardiotoxicity of DOX while strengthening its antitumor efficacy. Such a tumor-targeted albumin packaging strategy can also be applied to other antitumor drugs. Keywords: amino-terminal fragment of urokinase, urokinase receptor, drug carrier, human serum albumin, doxorubicin, cytotoxicity

  8. Efficacy of cognitive enhancers for Alzheimer’s disease: protocol for a systematic review and network meta-analysis

    Directory of Open Access Journals (Sweden)

    Tricco Andrea C

    2012-06-01

    Full Text Available Abstract Background Approximately 35 million people world-wide have Alzheimer’s disease and this is projected to nearly double by 2030. Cognitive enhancers, including cholinesterase inhibitors (for example, donepezil, galantamine and rivastigmine and memantine (N-methyl-D-aspartic acid (NMDA receptor antagonist have been approved for the treatment of Alzheimer’s disease in many countries. Our objective is to evaluate the comparative effectiveness, safety, and cost of cognitive enhancers for Alzheimer’s disease through a systematic review. Methods/design Studies examining the efficacy, safety, and cost of cognitive enhancers compared to placebo, supportive care, and other cognitive enhancers for Alzheimer’s patients will be included. The primary outcome is cognition and secondary outcomes include function, behavior, quality of life, safety, and cost. Experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, quasi-experimental studies (controlled before-after, interrupted time series, and observational studies (cohort, case–control studies will be eligible for inclusion. Inclusion will not be limited by publication status, time period or language of dissemination. We will search electronic databases (for example, MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Ageline from inception onwards. The electronic database search will be supplemented by searching for grey literature (for example, conference proceedings, searches in Google and relevant organization websites. Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational studies. If deemed appropriate, meta-analysis and network (that is, indirect

  9. Bifunctional Crosslinking Agents Enhance Anion Exchange Membrane Efficacy for Vanadium Redox Flow Batteries.

    Science.gov (United States)

    Wang, Wenpin; Xu, Min; Wang, Shubo; Xie, Xiaofeng; Lv, Yafei; Ramani, Vijay K

    2014-06-01

    A series of cross-linked fluorinated poly (aryl ether oxadiazole) membranes (FPAEOM) derivatized with imidazolium groups were prepared. Poly (N-vinylimidazole) (PVI) was used as the bifunctional cross-linking agent to: a) lower vanadium permeability, b) enhance dimensional stability, and c) concomitantly provide added ion exchange capacity in the resultant anion exchange membranes. At a molar ratio of PVI to FPAEOM of 1.5, the resultant membrane (FPAEOM-1.5 PVI) had an ion exchange capacity of 2.2 meq g-1, a vanadium permeability of 6.8×10-7 cm2 min-1, a water uptake of 68 wt.%, and an ionic conductivity of 22.0 mS cm-1, all at 25°C. Single cells prepared with the FPAEOM-1.5 PVI membrane exhibited a higher coulombic efficiency (> 92%) and energy efficiency (> 86%) after 40 test cycles in vanadium redox flow battery. The imidazolium cation showed high chemical stability in highly acidic and oxidizing vanadium solution as opposed to poor stability in alkaline solutions. Based on our DFT studies, this was attributed to the lower HOMO energy (-7.265 eV) of the HSO4- ion (compared to the OH- ion; -5.496 eV) and the larger HOMO-LUMO energy gap (6.394 eV) of dimethylimidazolium bisulfate ([DMIM] [HSO4]) as compared to [DMIM] [OH] (5.387 eV). PMID:24884171

  10. Rationale for a Multimodality Strategy to Enhance the Efficacy of Dendritic Cell-Based Cancer Immunotherapy.

    Science.gov (United States)

    Datta, Jashodeep; Berk, Erik; Cintolo, Jessica A; Xu, Shuwen; Roses, Robert E; Czerniecki, Brian J

    2015-01-01

    Dendritic cells (DC), master antigen-presenting cells that orchestrate interactions between the adaptive and innate immune arms, are increasingly utilized in cancer immunotherapy. Despite remarkable progress in our understanding of DC immunobiology, as well as several encouraging clinical applications - such as DC-based sipuleucel-T for metastatic castration-resistant prostate cancer - clinically effective DC-based immunotherapy as monotherapy for a majority of tumors remains a distant goal. The complex interplay between diverse molecular and immune processes that govern resistance to DC-based vaccination compels a multimodality approach, encompassing a growing arsenal of antitumor agents which target these distinct processes and synergistically enhance DC function. These include antibody-based targeted molecular therapies, immune checkpoint inhibitors, therapies that inhibit immunosuppressive cellular elements, conventional cytotoxic modalities, and immune potentiating adjuvants. It is likely that in the emerging era of "precision" cancer therapeutics, tangible clinical benefits will only be realized with a multifaceted - and personalized - approach combining DC-based vaccination with adjunctive strategies. PMID:26082780

  11. Rationale for a multimodality strategy to enhance the efficacy of dendritic cell-based cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Jashodeep eDatta

    2015-06-01

    Full Text Available Dendritic cells (DC, master antigen-presenting cells that orchestrate interactions between the adaptive and innate immune arms, are increasingly utilized in cancer immunotherapy. Despite remarkable progress in our understanding of DC immunobiology, as well as several encouraging clinical applications — such as DC-based sipuleucel-T for metastatic castration-resistant prostate cancer — clinically effective DC-based immunotherapy as monotherapy for a majority of tumors remains a distant goal. The complex interplay between diverse molecular and immune processes that govern resistance to DC-based vaccination compels a multimodality approach, encompassing a growing arsenal of antitumor agents which target these distinct processes and synergistically enhance DC function. These include antibody-based targeted molecular therapies, immune checkpoint inhibitors, therapies that inhibit immunosuppressive cellular elements, conventional cytotoxic modalities, and immune potentiating adjuvants. It is likely that in the emerging era of precision cancer therapeutics, tangible clinical benefits will only be realized with a multifaceted—and personalized—approach combining DC-based vaccination with adjunctive strategies.

  12. Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles

    Directory of Open Access Journals (Sweden)

    Mas N

    2014-05-01

    Full Text Available Núria Mas,1–3 Irene Galiana,3 Silvia Hurtado,† Laura Mondragón,1–3 Andrea Bernardos,1–3 Félix Sancenón,1–3 María D Marcos,1–3 Pedro Amorós,4 Nuria Abril-Utrillas,5 Ramón Martínez-Máñez,1–3 José Ramón Murguía1,3 1Centro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM, Centro Mixto Universidad Politécnica de Valencia, Universidad de Valencia, Valencia, Spain; 2Departamento de Química, Universidad Politécnica de Valencia, Valencia, Spain; 3CIBER de Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain; 4Institut de Ciència del Materials (ICMUV, Universitat de València, Valencia, Spain; 5Servicio Ginecología y Obstetricia, Hospital de la Plana, Vila-real, Spain†Silvia Hurtado passed away in September 2013 Abstract: pH-sensitive gated mesoporous silica nanoparticles have been synthesized. Increased extracellular pH and internalization into living yeast cells triggered molecular gate aperture and cargo release. Proper performance of the system was demonstrated with nanodevices loaded with fluorescein or with the antifungal agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole significantly enhanced tebuconazole cytotoxicity. As alterations of acidic external pH are a key parameter in the onset of fungal vaginitis, this nanodevice could improve the treatment for vaginal mycoses.Keywords: capped mesoporous nanoparticles, intracellular release, pH-responsive nanoparticles, Saccharomyces cerevisiae, tebuconazole loading

  13. Enhancing adolescent self-efficacy and collective efficacy through public engagement around HIV/AIDS competence: a multilevel, cluster randomized-controlled trial.

    Science.gov (United States)

    Carlson, Mary; Brennan, Robert T; Earls, Felton

    2012-09-01

    The potential capacity of children to confront the HIV/AIDS pandemic is rarely considered. Interventions to address the impact of the pandemic on children and adolescents commonly target only their vulnerabilities. We evaluated the Young Citizens Program, an adolescent-centered health promotion curriculum designed to increase self- and collective efficacy through public education and community mobilization across a municipality in the Kilimanjaro Region of Tanzania. The theoretical framework for the program integrates aspects of human capability, communicative action, social ecology and social cognition. The design consists of a cluster randomized-controlled trial (CRCT). Fifteen pairs of matched geopolitically defined neighborhoods of roughly 2000-4000 residents were randomly allocated to treatment and control arms. Within each neighborhood cluster, 24 randomly selected adolescents, ages 9-14, deliberated on topics of social ecology, citizenship, community health and HIV/AIDS competence. Building on their acquired understanding and confidence, they dramatized the scientific basis and social context of HIV infection, testing and treatment in their communities over a 28-week period. The curriculum comprised 5 modules: Group Formation, Understanding our Community, Health and our Community, Making Assessments and Taking Action in our Community and Inter-Acting in our Community. Adolescent participants and adult residents representative of their neighborhoods were surveyed before and after the intervention; data were analyzed using multilevel modeling. In treatment neighborhoods, adolescents increased their deliberative and communicative efficacy and adults showed higher collective efficacy for children. Following the CRCT assessments, the control group received the same curriculum. In the Kilimanjaro Region, the Young Citizens Program is becoming recognized as a structural, health promotion approach through which adolescent self-efficacy and child collective efficacy

  14. Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

    Directory of Open Access Journals (Sweden)

    Chen Hui-Ming

    2012-04-01

    effectively enhance anti-tumor potency of a gene-based cancer vaccine via the induction of RANTES expression at the skin immunization site.

  15. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    International Nuclear Information System (INIS)

    . Histologic studies confirmed that this combined treatment led to damage to both tumor vasculature and tumor cells. Importantly, the combined PDT treatment did not increase normal tissue damage and tissue recovered well at 60 days after treatment. Conclusions: Our results suggest that targeting both tumor vascular and cellular compartments by combining a long-interval PDT with a short-interval PDT can be an effective and safe way to enhance PDT damage to tumor tissue

  16. Pre-service teachers' knowledge of phonemic awareness: relationship to perceived knowledge, self-efficacy beliefs, and exposure to a multimedia-enhanced lecture.

    Science.gov (United States)

    Martinussen, Rhonda; Ferrari, Julia; Aitken, Madison; Willows, Dale

    2015-10-01

    This study examined the relations among perceived and actual knowledge of phonemic awareness (PA), exposure to PA instruction during practicum, and self-efficacy for teaching PA in a sample of 54 teacher candidates (TCs) enrolled in a 1-year Bachelor of Education program in a Canadian university. It also assessed the effects of a brief multimedia-enhanced lecture on TCs' actual knowledge of PA and efficacy ratings. Prior to the lecture, teacher candidates' scores on the PA assessment were relatively low with a mean percentage correct of 56.3%. Actual knowledge was not significantly correlated with perceived knowledge or self-efficacy ratings. Perceived knowledge was significantly and positively correlated with efficacy ratings and students' rating of their exposure to PA instruction during their practicum experience. A path analysis revealed that the relationship between exposure to PA instruction and self-efficacy beliefs was mediated by perceived knowledge controlling for actual knowledge and general prior experience working with young children. Analyses also revealed that TCs made significant gains in self-efficacy as well as actual knowledge when re-assessed after the lecture with a mean post-lecture score of 71.4%. Written feedback from the TCs indicated that the digital video clips included in the lecture provided clarity regarding the type of instructional practices that teachers could use to support phonemic awareness development in children. Implications for practice and future research on teacher preparation are discussed. PMID:26024995

  17. Wee1 inhibition by MK-1775 leads to tumor inhibition and enhances efficacy of gemcitabine in human sarcomas.

    Science.gov (United States)

    Kreahling, Jenny M; Foroutan, Parastou; Reed, Damon; Martinez, Gary; Razabdouski, Tiffany; Bui, Marilyn M; Raghavan, Meera; Letson, Douglas; Gillies, Robert J; Altiok, Soner

    2013-01-01

    Sarcomas are rare and heterogeneous mesenchymal tumors affecting both pediatric and adult populations with more than 70 recognized histologies. Doxorubicin and ifosfamide have been the main course of therapy for treatment of sarcomas; however, the response rate to these therapies is about 10-20% in metastatic setting. Toxicity with the drug combination is high, response rates remain low, and improvement in overall survival, especially in the metastatic disease, remains negligible and new agents are needed. Wee1 is a critical component of the G2/M cell cycle checkpoint control and mediates cell cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by MK1775 has been reported to enhance the cytotoxic effect of DNA damaging agents in different types of carcinomas. In this study we investigated the therapeutic efficacy of MK1775 in various sarcoma cell lines, patient-derived tumor explants ex vivo and in vivo both alone and in combination with gemcitabine, which is frequently used in the treatment of sarcomas. Our data demonstrate that MK1775 treatment as a single agent at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. Additionally, MK1775 significantly enhances the cytotoxic effect of gemcitabine in sarcoma cells lines with different p53 mutational status. In patient-derived bone and soft tissue sarcoma samples we showed that MK1775 alone and in combination with gemcitabine causes significant apoptotic cell death. Magnetic resonance imaging (MRI) and histopathologic studies showed that MK1775 induces significant cell death and terminal differentiation in a patient-derived xenograft mouse model of osteosarcoma in vivo. Our results together with the high safety profile of MK1775 strongly suggest that this drug can be used as a potential therapeutic agent in the treatment of both adult as well as pediatric sarcoma patients. PMID:23520471

  18. Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

    Science.gov (United States)

    De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

    2015-06-01

    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653). PMID:26691247

  19. Gracilaria lemaneiformis polysaccharide as integrin-targeting surface decorator of selenium nanoparticles to achieve enhanced anticancer efficacy.

    Science.gov (United States)

    Jiang, Wenting; Fu, Yuanting; Yang, Fang; Yang, Yufeng; Liu, Ting; Zheng, Wenjie; Zeng, Lilan; Chen, Tianfeng

    2014-08-27

    The poor permeability of glioma parenchyma represents a major limit for antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP), which has a high binding affinity to αvβ3 integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (SeNPs) to achieve antiglioblastoma efficacy. GLP-SeNPs showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. In U87 glioma cell membrane, which has a high integrin expression level, GLP-SeNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP-SeNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP-SeNPs was inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via αvβ3 integrin-mediated endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was enhanced significantly because of the induction of various apoptosis signaling pathways. Internalized GLP-SeNPs triggered intracellular reactive oxygen species downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance cell apoptosis. These findings suggest that surface decoration of nanomaterials with GLP could be an efficient strategy for design and preparation of glioblastoma targeting nanodrugs. PMID:25073123

  20. Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke; Kajikawa, Shu-hei [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Uesato, Shin-ichi [Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680 (Japan); Watanabe, Kazushi [Proubase Technology Inc., Kanagawa 211-0063 (Japan); Tanimura, Susumu [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Koji, Takehiko [Department of Histology and Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kohno, Michiaki, E-mail: kohnom@nagasaki-u.ac.jp [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Proubase Technology Inc., Kanagawa 211-0063 (Japan); Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501 (Japan)

    2013-04-19

    Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.

  1. Coating doxorubicin-loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmaniain hamsters by inducing Th1-type immune responses

    Science.gov (United States)

    Kansal, S; Tandon, R; Verma, A; Misra, P; Choudhary, A K; Verma, R; Verma, P R P; Dube, A; Mishra, P R

    2014-01-01

    Background and Purpose The aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(SA) coated nanocapsule (NCs) loaded with doxorubicin (SA-NCs-DOX) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (NE-DOX). Experimental Approach NE-DOX was prepared using low-energy emulsification methods. Stepwise addition of protamine sulphate and SA in a layer-by-layer manner was used to form SA-NCs-DOX. SA-NCs-DOX, NE-DOX and Free DOX were compared for their cytotoxicity against Leishmania donovani-infected macrophages in vitro and generation of T-cell responses in infected hamsters in vivo. Key Results Size and ζ potential of the NE-DOX and SA-NCs-DOX formulations were 310 ± 2.1 nm and (−)32.6 ± 2.1 mV, 342 ± 4.1 nm and (−)29.3 ± 1.2 mV respectively. SA-NCs-DOX was better (1.5 times) taken up by J774A.1 macrophages compared with NE-DOX. SA-NCs -DOX showed greater efficacy than NE-DOX against intramacrophagic amastigotes. SA-NCs-DOX treatment exhibited enhanced apoptotic efficiency than NE-DOX and free DOX as evident by cell cycle analysis, decrease in mitochondrial membrane potential, ROS and NO production. T-cell responses, when assessed through lymphoproliferative responses, NO production along with enhanced levels of iNOS, TNF-α, IFN-γ and IL-12 were found to be up-regulated after SA-NCs-DOX, compared with responses to NE-DOX in vivo. Parasitic burden was decreased in Leishmania-infected hamsters treated with SA-NCs-DOX, compared with NE-DOX. Conclusions and Implications Our results provide insights into the development of an alternative approach to improved management of leishmaniasis through a combination of chemotherapy with stimulation of the innate immune system. PMID:24837879

  2. Atorvastatin enhance efficacy of mesenchymal stem cells treatment for swine myocardial infarction via activation of nitric oxide synthase.

    Directory of Open Access Journals (Sweden)

    Lei Song

    Full Text Available BACKGROUND: In a swine model of acute myocardial infarction (AMI, Statins can enhance the therapeutic efficacy of mesenchymal stem cell (MSCs transplantation. However, the mechanisms remain unclear. This study aims at assessing whether atorvastatin (Ator facilitates the effects of MSCs through activation of nitric oxide synthase (NOS, especially endothelial nitric oxide synthase (eNOS, which is known to protect against ischemic injury. METHODS AND RESULTS: 42 miniswines were randomized into six groups (n = 7/group: Sham operation; AMI control; Ator only; MSC only, Ator+MSCs and Ator+MSCs+NG-nitrol-L-arginine (L-NNA, an inhibitor of NOS. In an open-heart surgery, swine coronary artery ligation and reperfusion model were established, and autologous bone-marrow MSCs were injected intramyocardium. Four weeks after transplantation, compared with the control group, Ator+MSCs animals exhibited decreased defect areas of both "perfusion" defined by Single-Photon Emission Computed Tomography (-6.2±1.8% vs. 2.0±5.1%, P = 0.0001 and "metabolism" defined by Positron Emission Tomography (-3.00±1.41% vs. 4.20±4.09%, P = 0.0004; Ejection fraction by Magnetic Resonance Imaging increased substantially (14.22±12.8% vs. 1.64±2.64%, P = 0.019. In addition, indices of inflammation, fibrosis, and apoptosis were reduced and survivals of MSCs or MSC-derived cells were increased in Ator+MSCs animals. In Ator or MSCs alone group, perfusion, metabolism, inflammation, fibrosis or apoptosis were reduced but there were no benefits in terms of heart function and cell survival. Furthermore, the above benefits of Ator+MSCs treatment could be partially blocked by L-NNA. CONCLUSIONS: Atorvastatin facilitates survival of implanted MSCs, improves function and morphology of infarcted hearts, mediated by activation of eNOS and alleviated by NOS inhibitor. The data reveal the cellular and molecular mechanism for anti-AMI therapy with a combination of statin and

  3. Additional gene therapy with Ad5CMV-p53 enhanced the efficacy of radiotherapy in human prostate cancer cells

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to investigate the efficacy of combination therapy of ionizing radiation (IR) and adenoviral p53 gene therapy and to evaluate its molecular mechanisms. Methods and Materials: Two human prostate cancer cell lines, DU145 and PC-3 cells, containing different types of p53 gene mutations, were investigated. The recombinant adenovirus vector containing the wild-type p53 gene (Ad5CMV-p53) was used for this study. Cells were irradiated (in 0, 2, 4, and 6 Gy, 300 cGy/min) and after 12 h of irradiation, the cells were infected with various doses of Ad5CMV-p53 (0-40 multiplicity of infection [MOI]). Cytotoxicity was determined by clonogenic assay. The molecular mechanisms were evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), apoptotic cell detection, and cell cycle analysis. Results: The cell growth inhibition in DU145 (p53-mutated) cells by IR was strongly enhanced by additional Ad5CMV-p53 infection in a viral dose-dependent manner. In DU145 cells, IR alone induced minimal p53 mRNA expression. However, IR combined with Ad5CMV-p53 infection stimulated significant increase in p53 mRNA expression supplemented with Bax and p21 mRNA expressions. In PC-3 (p53-null), IR induced Bax and p21 mRNA expression, while the combination effects were observed in p53, Bax, and p21 mRNA expression. Apoptotic cell deaths were rarely observed after IR alone (DU145: 3%, PC-3: 5%). However, after combination therapy, the proportion of apoptotic cells greatly increased (sevenfold in DU145 cells, and twice in PC-3 cells). G1 cell cycle arrest was observed after Ad5CMV-p53 infection and the combination in both cell lines. Conclusion: In this study, we demonstrated that the combination of IR and Ad5CMV-p53 gene therapy resulted in remarkable synergistic effects in human prostate cancer cells. This combination therapy could be one of the optimal treatment strategies for radioresistant prostate cancer

  4. iRGD decorated lipid-polymer hybrid nanoparticles for targeted co-delivery of doxorubicin and sorafenib to enhance anti-hepatocellular carcinoma efficacy.

    Science.gov (United States)

    Zhang, Jinming; Hu, Jie; Chan, Hon Fai; Skibba, Melissa; Liang, Guang; Chen, Meiwan

    2016-07-01

    The combination of doxorubicin (DOX) with sorafenib (SOR) has proven an effective strategy to enhance anti-hepatocellular carcinoma (HCC) efficacy. However, respective in vivo pharmacokinetic profiles and different endocytosis capacities of these two drugs greatly hinder their current application. Herein, the tumor-targeting peptide iRGD decorated lipid-polymer hybrid nanoparticles (NPs) with a shell-core structure were developed for co-delivery of DOX and SOR (DOX+SOR/iRGD NPs). After the drug ratio was optimized, the stabilized DOX+SOR/iRGD NPs were prepared. Through the iRGD-integrin recognition, DOX+SOR/iRGD NPs showed synergistic cytotoxicity, pro-apoptotic ability and enhanced internalization rate in human liver cancer HepG2 cells. In vivo pharmacokinetic result demonstrated that an extended circulation and bioavailability of DOX+SOR/iRGD NPs than free drugs. More importantly, DOX+SOR/iRGD NPs significantly enhanced antitumor efficiency in HCC xenograft mouse models. Overall, this study describes a promising nanoparticulate drug co-delivery strategy to combine clinical anticancer drugs and enhance anti-HCC efficacy. PMID:26964482

  5. Technology-Enhanced Maintenance of Treatment Gains in Eating Disorders: Efficacy of an Intervention Delivered via Text Messaging

    Science.gov (United States)

    Bauer, Stephanie; Okon, Eberhard; Meermann, Rolf; Kordy, Hans

    2012-01-01

    Objective: Given the lack of maintenance interventions for eating disorders, a program delivered via the short message service (SMS) and text messaging was developed to support patients after their discharge from inpatient treatment. Method: The efficacy of the intervention was studied in a randomized controlled trial. Additionally, its impact on…

  6. Limits of PowerPoint's Power: Enhancing Students' Self-Efficacy and Attitudes but Not Their Behavior

    Science.gov (United States)

    Susskind, Joshua E.

    2008-01-01

    The effects of accompanying lectures with computer-mediated PowerPoint presentations or PowerPoint generated overheads on students' self-efficacy, attitudes, course performance, and class-related behaviors were examined. Two Introduction to Developmental Psychology sections were initially taught with lectures accompanied by either overheads or…

  7. Efficacy of an Integrated School Curriculum Pedometer Intervention to Enhance Physical Activity and to Reduce Weight Status in Children

    Science.gov (United States)

    Duncan, Michael; Birch, Samantha; Woodfield, Lorayne

    2012-01-01

    The purpose of this study was to examine the efficacy of an integrated school curriculum pedometer intervention on children's physical activity and weight status. Following ethics approval and informed consent, 59 children (22 boys, 27 girls, aged 10-11) from a primary school in central England completed a four-week integrated physical activity…

  8. Safety, Tolerance, and Enhanced Efficacy of a Bioavailable Formulation of Curcumin With Fenugreek Dietary Fiber on Occupational Stress: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

    Science.gov (United States)

    Pandaran Sudheeran, Subash; Jacob, Della; Natinga Mulakal, Johannah; Gopinathan Nair, Gopakumar; Maliakel, Abhilash; Maliakel, Balu; Kuttan, Ramadasan; Im, Krishnakumar

    2016-06-01

    Drug delivery systems capable of delivering free (unconjugated) curcuminoids is of great therapeutic significance, since the absorption of bioactive and permeable form plays a key factor in mediating the efficacy of a substance which undergoes rapid biotransformation. Considering the recent understanding on the relatively high bioactivities and blood-brain-barrier permeability of free curcuminoids over their conjugated metabolites, the present human study investigated the safety, antioxidant efficacy, and bioavailability of CurQfen (curcumagalactomannoside [CGM]), a food-grade formulation of natural curcumin with fenugreek dietary fiber that has shown to possess improved blood-brain-barrier permeability and tissue distribution in rats. In this randomized double-blinded and placebo-controlled trial, 60 subjects experiencing occupational stress-related anxiety and fatigue were randomized to receive CGM, standard curcumin, and placebo for 30 days (500 mg twice daily). The study demonstrated the safety, tolerance, and enhanced efficacy of CGM in comparison with unformulated standard curcumin. A significant improvement in the quality of life (P < 0.05) with considerable reduction in stress (P < 0.001), anxiety (P < 0.001), and fatigue (P < 0.001) was observed among CGM-treated subjects as compared with the standard curcumin group, when monitored by SF-36, Perceived Stress Scale with 14 items, and Beck Anxiety Inventory scores. Improvement in the quality of life was further correlated with the significant enhancement in endogenous antioxidant markers (P < 0.01) and reduction in lipid peroxidation (P < 0.001). Further comparison of the free curcuminoids bioavailability after a single-dose (500 mg once per day) and repeated-dose (500 mg twice daily for 30 days) oral administration revealed enhanced absorption and improved pharmacokinetics of CGM upon both single- (30.7-fold) and repeated-dose (39.1-fold) administrations. PMID:27043120

  9. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions

    International Nuclear Information System (INIS)

    A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT. (orig.)

  10. Nanodrug-Enhanced Radiofrequency Tumor Ablation: Effect of Micellar or Liposomal Carrier on Drug Delivery and Treatment Efficacy

    OpenAIRE

    Moussa, Marwan; Goldberg, S. Nahum; Kumar, Gaurav; Sawant, Rupa R.; Levchenko, Tatyana; Torchilin, Vladimir P.; Ahmed, Muneeb

    2014-01-01

    Purpose To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. Materials/Methods Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of IV fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4–24 hr. Next, to study carrier type on drug efficiency, RF...

  11. Nanodrug-Enhanced Radiofrequency Tumor Ablation: Effect of Micellar or Liposomal Carrier on Drug Delivery and Treatment Efficacy

    OpenAIRE

    Marwan Moussa; S Nahum Goldberg; Gaurav Kumar; Sawant, Rupa R.; Tatyana Levchenko; Torchilin, Vladimir P.; Muneeb Ahmed

    2014-01-01

    PURPOSE: To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. MATERIALS/METHODS: Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency...

  12. Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy

    OpenAIRE

    Johnson, Leisa; Huseni, Mahrukh; Smyczek, Tanya; Lima, Anthony; Yeung, Stacey; Cheng, Jason H.; Molina, Rafael; Kan, David; De Mazière, Ann; Klumperman, Judith; Kasman, Ian; Zhang, Yin; Dennis, Mark S; Eastham-Anderson, Jeffrey; Jubb, Adrian M.

    2013-01-01

    Many oncology drugs are administered at their maximally tolerated dose without the knowledge of their optimal efficacious dose range. In this study, we describe a multifaceted approach that integrated preclinical and clinical data to identify the optimal dose for an antiangiogenesis agent, anti-EGFL7. EGFL7 is an extracellular matrix–associated protein expressed in activated endothelium. Recombinant EGFL7 protein supported EC adhesion and protected ECs from stress-induced apoptosis. Anti-EGFL...

  13. Using Robotics and Game Design to Enhance Children's Self-Efficacy, STEM Attitudes, and Computational Thinking Skills

    Science.gov (United States)

    Leonard, Jacqueline; Buss, Alan; Gamboa, Ruben; Mitchell, Monica; Fashola, Olatokunbo S.; Hubert, Tarcia; Almughyirah, Sultan

    2016-06-01

    This paper describes the findings of a pilot study that used robotics and game design to develop middle school students' computational thinking strategies. One hundred and twenty-four students engaged in LEGO® EV3 robotics and created games using Scalable Game Design software. The results of the study revealed students' pre-post self-efficacy scores on the construct of computer use declined significantly, while the constructs of videogaming and computer gaming remained unchanged. When these constructs were analyzed by type of learning environment, self-efficacy on videogaming increased significantly in the combined robotics/gaming environment compared with the gaming-only context. Student attitudes toward STEM, however, did not change significantly as a result of the study. Finally, children's computational thinking (CT) strategies varied by method of instruction as students who participated in holistic game development (i.e., Project First) had higher CT ratings. This study contributes to the STEM education literature on the use of robotics and game design to influence self-efficacy in technology and CT, while informing the research team about the adaptations needed to ensure project fidelity during the remaining years of the study.

  14. Combination therapy with BMP-2 and BMSCs enhances bone healing efficacy of PCL scaffold fabricated using the 3D plotting system in a large segmental defect model.

    Science.gov (United States)

    Kang, Sun-Woong; Bae, Ji-Hoon; Park, Su-A; Kim, Wan-Doo; Park, Mi-Su; Ko, You-Jin; Jang, Hyon-Seok; Park, Jung-Ho

    2012-07-01

    The three-dimensional (3D) plotting system is a rapidly-developing scaffold fabrication method for bone tissue engineering. It yields a highly porous and inter-connective structure without the use of cytotoxic solvents. However, the therapeutic effects of a scaffold fabricated using the 3D plotting system in a large segmental defect model have not yet been demonstrated. We have tested two hypotheses: whether the bone healing efficacy of scaffold fabricated using the 3D plotting system would be enhanced by bone marrow-derived mesenchymal stem cell (BMSC) transplantation; and whether the combination of bone morphogenetic protein-2 (BMP-2) administration and BMSC transplantation onto the scaffold would act synergistically to enhance bone regeneration in a large segmental defect model. The use of the combined therapy did increase bone regeneration further as compared to that with monotherapy in large segmental bone defects. PMID:22447098

  15. The role of intrinsic motivation in a group of low vision patients participating in a self-management programme to enhance self-efficacy and quality of life.

    Science.gov (United States)

    Tay, Kay Chai Peter; Drury, Vicki Blair; Mackey, Sandra

    2014-02-01

    Self-management programmes have previously been found to decrease health problems, enhance quality of life and increase independence. However, there is no literature that examines the influence of the participants' intrinsic motivation on the outcomes of such programmes. This study examined the role of intrinsic motivation in a pilot low vision self-management programme to enhance self-efficacy and quality of life of the programme participants. A positive association was observed between the female participants' perceived choice and perceived competence, two underlying dimensions of the Intrinsic Motivation Inventory. In addition, a positive correlation was observed between the younger participants' perceived competence and the change in their quality of life. The findings provide some support for consideration of participants' intrinsic motivation in the development of effective self-management programmes. PMID:24580971

  16. CpG-A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations

    NARCIS (Netherlands)

    H.H. van Ojik; L. Bevaart; C.E. Dahle; A. Bakker (Annie); M.J.H. Jansen (Marco); M.J. van Vugt; J.G. van de Winkel; G.J. Weiner

    2003-01-01

    textabstractImmunostimulatory CpG oligodeoxynucleotides (ODNs) can enhance the therapeutic effect of monoclonal antibodies (mAbs) by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Distinct classes of CpG ODNs have been found recently to stimulate different effector

  17. The combination of Pleurotus ferulae water extract and CpG-ODN enhances the immune responses and antitumor efficacy of HPV peptides pulsed dendritic cell-based vaccine.

    Science.gov (United States)

    Li, Jinyu; Li, Jinyao; Aipire, Adila; Luo, JiaoJiao; Yuan, Pengfei; Zhang, Fuchun

    2016-06-30

    Our previous study reported that the combination of Pleurotus ferulae water extract (PFWE) and CpG (PFWE+CpG) enhanced the maturation and function of dendritic cells (DCs). Here, we investigated the effects of PFWE+CpG on the immune responses and antitumor efficacy of DC-based vaccine. We observed that all of HPV E6 and E7 peptides pulsed DCs (HPV-immature DCs, HPV+PFWE-, +CpG- or +PFWE+CpG-DCs) induced antigen-specific CD8(+) T cell responses and HPV+PFWE+CpG-DCs induced highest level of CD8(+) T cell responses. The antitumor efficacy of HPV-DCs vaccines was evaluated in TC-1 tumor mouse model. The early therapeutic study showed that HPV+PFWE-, +CpG- and +PFWE+CpG-DCs greatly inhibited tumor growth. Moreover, HPV+PFWE+CpG-DCs controlled tumor growth at a faster rate compared to other groups. These three groups induced HPV-specific CD8(+) T cell responses and significantly decreased the frequencies of induced regulatory T cells (iTregs: CD4(+)CD25(-)Fopx3(+)). However, only HPV+PFWE+CpG-DCs significantly decreased the frequency of natural Tregs (nTregs: CD4(+)CD25(+)Fopx3(+)). Furthermore, HPV+PFWE+CpG-DCs also significantly inhibited tumor growth in the late therapeutic study. The results showed that PFWE+CpG enhanced the immune responses and antitumor efficacy of DC-based vaccine, suggesting that PFWE+CpG might be the potential candidate for the generation of clinical-grade mature DCs. PMID:27211038

  18. CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine

    OpenAIRE

    Kumar, Sanjai; Jones, Trevor R.; Oakley, Miranda S.; Zheng, Hong; Shanmuga P Kuppusamy; Taye, Alem; Krieg, Arthur M.; Stowers, Anthony W; Kaslow, David C.; Hoffman, Stephen L.

    2004-01-01

    Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the adjuvant effect of murine CpG ODN 1826 on the immunogenicity and protective efficacy of the Saccharomyces cerevisiae-expressed 19-kDa C-terminal region of merozoite surface protein 1 (yMSP119) of the murine malaria parasite Plasmodium yoelii. We found that in C57BL/6 mice, following sporozoite challe...

  19. CpG adjuvant enhances the mucosal immunogenicity and efficacy of a Treponema pallidum DNA vaccine in rabbits

    Science.gov (United States)

    Zhao, Feijun; Liu, Shuangquan; Zhang, Xiaohong; Yu, Jian; Zeng, Tiebing; Gu, Weiming; Cao, Xunyu; Chen, Xi; Wu, Yimou

    2013-01-01

    Objectives: The protective response against Treponema pallidum (Tp) infection of a DNA vaccine enhanced by an adjuvant CpG ODN was investigated. Results: The mucosal adjuvant CpG ODN enhanced the production of higher levels of anti-TpGpd antibodies induced by pcD/Gpd-IL-2 in rabbits. It also resulted in higher levels of secretion of IL-2 and IFN-γ, and facilitated T cell proliferation and differentiation (p 0.05). Furthermore, CpG ODN stimulated the production of mucosa-specific anti-sIgA antibodies and resulted in the lowest Tp-positive rate (6.7%) for Tp-infection of skin lesions and the lowest rates (8.3%) of ulceration lesions, thus achieving better protective effects. Methods: New Zealand rabbits were immunized with the eukaryotic vector encoding recombinant pcD/Gpd-IL-2 using intramuscular multi-injection or together with mucosal enhancement via a nasal route. The effect of the mucosal adjuvant CpG ODN was examined. Conclusions:The CpG ODN adjuvant significantly enhances the humoral and cellular immune effects of the immunization by pcD/Gpd-IL-2 with mucosal enhancement via nasal route. It also stimulates strong mucosal immune effects, thus initiating more efficient immune-protective effects. PMID:23563515

  20. Enhanced antitumoral efficacy and immune response following conditionally replicative adenovirus containing constitutive HSF1 delivery to rodent tumors

    Directory of Open Access Journals (Sweden)

    Fan Rong

    2012-05-01

    Full Text Available Abstract Background Oncolytic adenoviruses are promising as anticancer agents but have limited clinical responses. Our previous study showed that heat shock transcription factor 1 (HSF1 overexpression could increase the anti-tumor efficacy of E1B55kD deleted oncolytic adenovirus through increasing the viral burst. Due to the important roles of heat shock proteins (HSPs in eliciting innate and adaptive immunity, we reasoned that besides increasing the viral burst, HSF1 may also play a role in increasing tumor specific immune response. Methods In the present study, intra-dermal murine models of melanoma (B16 and colorectal carcinoma (CT26 were treated with E1B55kD deleted oncolytic adenovirus Adel55 or Adel55 incorporated with cHSF1, HSF1i, HSP70, or HSP90 by intra-tumoral injection. Tumors were surgically excised 72 h post injection and animals were analyzed for tumor resistance and survival rate. Results Approximately 95% of animals in the Adel55-cHSF1 treated group showed sustained resistance upon re-challenge with autologous tumor cells, but not in PBS, Adel55, or Adel55-HSF1i treated groups. Only 50–65% animals in the Adel55-HSP70 and Adel55-HSP90 treated group showed tumor resistance. Tumor resistance was associated with development of tumor type specific cellular immune responses. Adel55-cHSF1 treatment also showed higher efficacy in diminishing progression of the secondary tumor focus than Adel55-HSP70 or Adel55-HSP90 treatment. Conclusions Besides by increasing its burst in tumor cells, cHSF1 could also augment the potential of E1B55kD deleted oncolytic adenovirus by increasing the tumor-specific immune response, which is beneficial to prevent tumor recurrence. cHSF1 is a better gene for neoadjuvant immunotherapy than other heat shock protein genes.

  1. Marine-Derived Quorum-Sensing Inhibitory Activities Enhance the Antibacterial Efficacy of Tobramycin against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Alessandro Busetti

    2014-12-01

    Full Text Available Bacterial epiphytes isolated from marine eukaryotes were screened for the production of quorum sensing inhibitory compounds (QSIs. Marine isolate KS8, identified as a Pseudoalteromonas sp., was found to display strong quorum sensing inhibitory (QSI activity against acyl homoserine lactone (AHL-based reporter strains Chromobacterium violaceum ATCC 12472 and CV026. KS8 supernatant significantly reduced biofilm biomass during biofilm formation (−63% and in pre-established, mature P. aeruginosa PAO1 biofilms (−33%. KS8 supernatant also caused a 0.97-log reduction (−89% and a 2-log reduction (−99% in PAO1 biofilm viable counts in the biofilm formation assay and the biofilm eradication assay respectively. The crude organic extract of KS8 had a minimum inhibitory concentration (MIC of 2 mg/mL against PAO1 but no minimum bactericidal concentration (MBC was observed over the concentration range tested (MBC > 16 mg/mL. Sub-MIC concentrations (1 mg/mL of KS8 crude organic extract significantly reduced the quorum sensing (QS-dependent production of both pyoverdin and pyocyanin in P. aeruginosa PAO1 without affecting growth. A combinatorial approach using tobramycin and the crude organic extract at 1 mg/mL against planktonic P. aeruginosa PAO1 was found to increase the efficacy of tobramycin ten-fold, decreasing the MIC from 0.75 to 0.075 µg/mL. These data support the validity of approaches combining conventional antibiotic therapy with non-antibiotic compounds to improve the efficacy of current treatments.

  2. Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy: a mathematical model.

    Directory of Open Access Journals (Sweden)

    Yangjin Kim

    Full Text Available Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV. We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.

  3. Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy: a mathematical model.

    Science.gov (United States)

    Kim, Yangjin; Lee, Hyun Geun; Dmitrieva, Nina; Kim, Junseok; Kaur, Balveen; Friedman, Avner

    2014-01-01

    Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment. PMID:25047810

  4. Doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against HER 2/neu in a murine mammary carcinoma model

    International Nuclear Information System (INIS)

    The purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines. Mice were injected in the mammary fat pad with an aggressive breast tumor cell line that expresses HER2/neu. The mice were treated 3 days later with a noncurative dose of either doxorubicin or paclitaxel, and the following day with a gene vaccine to HER2/neu. Two more doses of vaccine were given 14 days apart. Two types of gene vaccines were tested: a plasmid vaccine encoding a self-replicating RNA (replicon) of Sindbis virus (SINCP), in which the viral structural proteins were replaced by the gene for neu; and a viral replicon particle derived from an attenuated strain of Venezuelan equine encephalitis virus, containing a replicon RNA in which the Venezuelan equine encephalitis virus structural proteins were replaced by the gene for neu. Neither vaccination alone nor chemotherapy alone significantly reduced the growth of the mammary carcinoma. In contrast, chemotherapy followed by vaccination reduced tumor growth by a small, but significant amount. Antigen-specific CD8+ T lymphocytes were induced by the combined treatment, indicating that the control of tumor growth was most probably due to an immunological mechanism. The results demonstrated that doxorubicin and paclitaxel, commonly used chemotherapeutic agents for the treatment of breast cancer, when used at immunomodulating doses augmented the antitumor efficacy of gene vaccines directed against HER2/neu. The combination of chemotherapeutic agents plus vaccine immunotherapy may induce a tumor-specific immune response that could be beneficial for the adjuvant treatment of patients with minimal residual disease. The regimen warrants further evaluation in a clinical setting

  5. The efficacy of contrast-enhanced T1-weighted MR imaging of the lumbar spine in rheumatoid arthritis patients

    International Nuclear Information System (INIS)

    We investigated MR imaging of the lumbar spine in rheumatoid arthritis (RA) patients, including T1-weighted, T2-weighted, and contrast enhanced T1-weighted MR imaging in 20 patients with rheumatoid arthritis and in 23 controls. Lesions were found at spinous processes, facet joints, spinal bodies, end plates, and the limbus of spinal bodies. At least one lesion was found in 18 patients, and notably, 70% of patients had lesions in the spinous process and 75% of patients in the facet joints. The fat-suppression contrast-enhanced T1-weighted MR was very useful in lumbar lesions in RA patients. (author)

  6. Social support seeking and self-efficacy-building strategies in enhancing the emotional well-being of informal HIV/AIDS caregivers in Ibadan, Oyo state, Nigeria.

    Science.gov (United States)

    Okeke, Bernedette Okwuchukwu

    2016-01-01

    This study examined the relative efficacy of social support seeking (SSS) and self-efficacy building (SEB) in the management of emotional well-being of caregivers of people suffering from HIV/AIDS. It was based at the United States President's Emergency Plan for AIDS Relief (PEPFAR) center in the University College Hospital, Ibadan, Oyo state, being the first and the largest teaching hospital in Nigeria. A 3 × 2 factorial design consisting of treatment and a control group was used. The columns have two levels of gender being male and female caregivers. One-hundred and sixty-five (165) caregivers who were taking care of people that are suffering from HIV/AIDS were purposively selected and randomly assigned to the treatment groups and control. The treatment was carried out for a period of eight weeks. Two null hypotheses were tested, both at .05 levels of significance. Data were collected with the use of standardized intruments rating scale; social support scale, general self-efficacy scale and emotional well-being scale. ANCOVA was used to establish significant treatment effects with the pretest as covariate. Even though SSS and SEB were both found to be effective in enhancing the emotional well-being of informal caregivers in this study when compared to the controls, SSS was significantly more effective than SEB in achieving this goal. Since the HIV/AIDS patients cannot be adequately cared for in the hospital settings due to severe shortages of material, personnel and time, serious efforts should be made by the three levels of the health care system viz: the primary, secondary and tertiary health care systems, to encourage the employment of the psychological management of caregivers of people suffering from HIV/AIDS. Also, the psychologists, clinical psychologists and the significant others should be encouraged to employ this psychological management in the care of HIV/AIDS informal caregivers. PMID:26831832

  7. The diagnostic efficacy of quantitative liver MR imaging with diffusion-weighted, SWI, and hepato-specific contrast-enhanced sequences in staging liver fibrosis - a multiparametric approach

    Energy Technology Data Exchange (ETDEWEB)

    Feier, Diana [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Emergency County Hospital, Department of Radiology, Cluj-Napoca (Romania); Balassy, Csilla; Bastati, Nina; Fragner, Romana; Ba-Ssalamah, Ahmed [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Wrba, Friedrich [Medical University of Vienna, General Hospital of Vienna (AKH), Department of Pathology, Vienna (Austria)

    2016-02-15

    To assess the diagnostic efficacy of multiparametric MRI using quantitative measurements of the apparent diffusion coefficient (ADC) of the liver parenchyma on diffusion-weighted imaging (DWI), signal intensity (SI) on susceptibility-weighted imaging (SWI), and gadoxetic acid-enhanced T1-weighted imaging during the hepatobiliary phase for the staging of liver fibrosis. Seventy-seven patients underwent a 3T MRI examination, including DWI/SWI sequences and gadoxetic acid-enhanced T1-weighted MRI. Liver fibrosis according to liver biopsy was staged using the Metavir fibrosis score: F0 (n = 21, 27.3 %); F1 (n = 7, 9.1 %); F2 (n = 8, 10.4 %); F3 (n = 12, 15.6 %); and F4 (n = 29, 37.7 %). SI of the liver was defined using region-of-interest measurements to calculate the ADC values, the relative enhancement (RE) in the hepatobiliary phase, and the liver-to-muscle ratio (LMR) measurements for SWI. The values of RE, LMR, and ADC measurements were statistically significantly different among the five fibrosis stages (p < 0.004). Combining the three parameters in a multiparametric approach, the AUC for detecting F1 stage or greater (≥ F1) was 94 %, for F2 or greater (≥F2) was 95 %, for F3 or greater (≥F3) was 90 %, and for stage F4 was 93 %. Multiparametric MRI is an efficient non-invasive diagnostic tool for the staging of liver fibrosis. (orig.)

  8. Multicenter phase-II trial of safety and efficacy of NC100150 for steady-state contrast-enhanced peripheral magnetic resonance angiography

    International Nuclear Information System (INIS)

    The aim of this study was to test the safety and efficacy of NC100150 injection for steady-state contrast-enhanced peripheral MR angiography in a multicentre phase-II trial. Thirty-three patients underwent steady-state NC100150 enhanced MR angiography (5 mg Fe/kg body weight) of the aortoiliac and femoropopliteal arteries. Safety assessment consisted of pre- and post-injection (2, 24 and 72 h) monitoring of vital signs, physical examination as well as laboratory and electrocardiographic parameters. To determine sensitivity and specificity for detection of haemodynamically significant stenoses (HSS; >50% reduction of luminal diameter) MR angiograms were compared with intra-arterial digital subtraction angiography (IA DSA), which was considered the standard of reference. In 33 patients a mean of 12.8 ml NC100150 was injected. Eleven patients reported 13 mild and 2 moderate adverse events. Five mild and one moderate adverse event were considered due to NC100150 injection. There were no significant changes in vital signs, laboratory or electrocardiographic parameters. Sensitivity and specificity (in percent) for detection of HSS were 87 and 64, 56 and 76, and 75 and 84, for iliac, femoral and popliteal arteries, respectively. NC100150 high-resolution steady-state MR angiography can be performed safely and is feasible for the detection of peripheral arterial HSS, but is as yet not a clinically useful alternative to conventional gadolinium-enhanced MR angiography. (orig.)

  9. The diagnostic efficacy of quantitative liver MR imaging with diffusion-weighted, SWI, and hepato-specific contrast-enhanced sequences in staging liver fibrosis - a multiparametric approach

    International Nuclear Information System (INIS)

    To assess the diagnostic efficacy of multiparametric MRI using quantitative measurements of the apparent diffusion coefficient (ADC) of the liver parenchyma on diffusion-weighted imaging (DWI), signal intensity (SI) on susceptibility-weighted imaging (SWI), and gadoxetic acid-enhanced T1-weighted imaging during the hepatobiliary phase for the staging of liver fibrosis. Seventy-seven patients underwent a 3T MRI examination, including DWI/SWI sequences and gadoxetic acid-enhanced T1-weighted MRI. Liver fibrosis according to liver biopsy was staged using the Metavir fibrosis score: F0 (n = 21, 27.3 %); F1 (n = 7, 9.1 %); F2 (n = 8, 10.4 %); F3 (n = 12, 15.6 %); and F4 (n = 29, 37.7 %). SI of the liver was defined using region-of-interest measurements to calculate the ADC values, the relative enhancement (RE) in the hepatobiliary phase, and the liver-to-muscle ratio (LMR) measurements for SWI. The values of RE, LMR, and ADC measurements were statistically significantly different among the five fibrosis stages (p < 0.004). Combining the three parameters in a multiparametric approach, the AUC for detecting F1 stage or greater (≥ F1) was 94 %, for F2 or greater (≥F2) was 95 %, for F3 or greater (≥F3) was 90 %, and for stage F4 was 93 %. Multiparametric MRI is an efficient non-invasive diagnostic tool for the staging of liver fibrosis. (orig.)

  10. Use of Xylitol To Enhance the Therapeutic Efficacy of Polymethylmethacrylate-Based Antibiotic Therapy in Treatment of Chronic Osteomyelitis

    Science.gov (United States)

    Beenken, Karen E.; Bradney, Laura; Bellamy, William; Skinner, Robert A.; McLaren, Sandra G.; Gruenwald, M. Johannes; Spencer, Horace J.; Smith, James K.; Haggard, Warren O.

    2012-01-01

    Using a rabbit model of postsurgical osteomyelitis, we demonstrate that incorporation of xylitol into polymethylmethacrylate (PMMA) bone cement enhances the elution of daptomycin under in vivo conditions. We also demonstrate that this can be correlated with an improved therapeutic outcome in the treatment of a chronic bone infection following surgical debridement. PMID:22948866

  11. Use of Xylitol To Enhance the Therapeutic Efficacy of Polymethylmethacrylate-Based Antibiotic Therapy in Treatment of Chronic Osteomyelitis

    OpenAIRE

    Beenken, Karen E.; Bradney, Laura; Bellamy, William; Skinner, Robert A.; McLaren, Sandra G.; Gruenwald, M. Johannes; Spencer, Horace J.; Smith, James K; Haggard, Warren O.; Smeltzer, Mark S.

    2012-01-01

    Using a rabbit model of postsurgical osteomyelitis, we demonstrate that incorporation of xylitol into polymethylmethacrylate (PMMA) bone cement enhances the elution of daptomycin under in vivo conditions. We also demonstrate that this can be correlated with an improved therapeutic outcome in the treatment of a chronic bone infection following surgical debridement.

  12. Strontium-doped calcium polyphosphate/ultrahigh molecular weight polyethylene composites: A new class of artificial joint components with enhanced biological efficacy to aseptic loosening.

    Science.gov (United States)

    Gu, Zhipeng; Huang, Bingxue; Li, Yiwen; Tian, Meng; Li, Li; Yu, Xixun

    2016-04-01

    To enhance implant stability and prolong the service life of artificial joint component, a new approach was proposed to improve the wear resistance of artificial joint component and endow artificial joint component with the biological efficacy of resistance to aseptic loosening. Strontium calcium polyphosphate (SCPP) were interfused in ultrahigh molecular weight polyethylene (UHMWPE) by a combination of liquid nitrogen ball-milling and flat-panel curing process to prepare the SCPP/UHMWPE composites. The micro-structure, mechanical characterization, tribological characterization and bioactivities of various SCPP/UHMWPE composites were investigated. The results suggested that this method could statistically improve the wear resistance of UHMWPE resulting from a good SCPP particle dispersion. Moreover, it is also observed that the SCPP/UHMWPE composites-wear particles could promote the production of OPG by osteoblasts and decrease the production of RANKL by osteoblasts, and then increase the OPG/RANKL ratio. This indicated that the SCPP/UHMWPE composites had potential efficacy to prevent and treat aseptic loosening. Above all, the SCPP/UHMWPE composites with a suitable SCPP content would be the promising materials for fabricating artificial joint component with ability to resist aseptic loosening. PMID:26838880

  13. Comparison of pre- and/or postphotodynamic therapy and intense pulsed light treatment protocols for the reduction of postprocedure-associated symptoms and enhancement of therapeutic efficacy.

    Science.gov (United States)

    Garcia, Barbara D; Goldman, Mitchel P; Gold, Michael H

    2007-09-01

    Photodynamic therapy (PDT) and intense pulsed light therapy (IPL) are commonly used in the setting of photorejuvenation. Patient expectations for minimal to no downtime associated with these procedures has become an increasingly important issue. In an attempt to define a topical skin care regimen that would reduce procedure-related symptoms and possibly enhance therapeutic efficacy, 4 separate topical products were examined. Avène Thermal Spring Water (Laboratoires Dermatologiques Avène, Les Cauquillous, France), NIA 24 (Niadyne, Inc, Research Triangle Park, NC), MimyX cream (Stiefel Laboratories, Coral Gables, FL), and Biafine (OrthoNeutrogena, Los Angeles, CA) were studied individually in the setting of either PDT or IPL treatments. The results of these studies indicate that a pre- and/or postprocedure topical skin care regimen can be beneficial in reducing postprocedure symptoms. PMID:17941364

  14. Influence of penetration enhancers and molecular weight in antifungals permeation through bovine hoof membranes and prediction of efficacy in human nails.

    Science.gov (United States)

    Miron, D; Cornelio, R; Troleis, J; Mariath, J; Zimmer, A R; Mayorga, P; Schapoval, E E S

    2014-01-23

    This work aimed to evaluate the effect of different substances on the permeation of geraniol through bovine hoof membranes. Different penetration enhancers were able to increase the permeability up to 25 times compared to control. It was demonstrated that acetilcysteine in association with ascorbic acid increased the permeation, even in acid formulations. In addition, some antifungal drugs were incorporated into a gel formulation of HPMC containing acetylcysteine 5% and ascorbic acid 0.2% and then the permeation coefficient through bovine hoof membranes was evaluated. The relationship between permeability and molecular weight was established for fluconazole, miconazole, terbinafine, butenafine, geraniol and nerol. Geraniol and nerol, the antifungals with lower molecular weight, had the better permeability results. Permeability coefficients for nail plates were estimated and geraniol demonstrated similar or even better efficacy index values against T. rubrum, T. menthagrophytes and M. canis compared with terbinafine and miconazole. PMID:23999034

  15. A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

    Science.gov (United States)

    Fonseca, Jairo Andres; Cabrera-Mora, Monica; Kashentseva, Elena A; Villegas, John Paul; Fernandez, Alejandra; Van Pelt, Amelia; Dmitriev, Igor P; Curiel, David T; Moreno, Alberto

    2016-01-01

    A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR) of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity and protective

  16. Enhanced therapeutic efficacy of vitamin K2 by silencing BCL-2 expression in SMMC-7721 hepatocellular carcinoma cells

    OpenAIRE

    Yao, Yuting; Li, Lu; Zhang, He; Jia, Renbing; Liu, Bo; Zhao, Xiaoping; ZHANG, LEILEI; QIAN, GUANXIANG; Fan, Xianqun; Ge, Shengfang

    2012-01-01

    Vitamin K2 (VK2) exerts cell growth inhibitory effects in various human cancer cells such as SMMC-7721 hepatocellular carcinoma (HCC) cells. BCL-2 is an antiapoptotic protein that is frequently overexpressed in numerous tumors. Modulation of multiple antiapoptotic signaling pathways involving BCL-2, which are related to growth factor-stimulated signal transduction in cell survival, is essential for enhancement of the cytotoxic effect of anticancer drugs. In this study, we tested a new strateg...

  17. Structure-based optimization of GRP78-binding peptides that enhances efficacy in cancer imaging and therapy.

    Science.gov (United States)

    Wang, Sheng-Hung; Lee, Andy Chi-Lung; Chen, I-Ju; Chang, Nai-Chuan; Wu, Han-Chung; Yu, Hui-Ming; Chang, Ya-Jen; Lee, Te-Wei; Yu, Jyh-Cherng; Yu, Alice L; Yu, John

    2016-07-01

    It is more challenging to design peptide drugs than small molecules through molecular docking and in silico analysis. Here, we developed a structure-based approach with various computational and analytical techniques to optimize cancer-targeting peptides for molecular imaging and therapy. We first utilized a peptide-binding protein database to identify GRP78, a specific cancer cell-surface marker, as a target protein for the lead, L-peptide. Subsequently, we used homologous modeling and molecular docking to identify a peptide-binding domain within GRP78 and optimized a series of peptides with a new protein-ligand scoring program, HotLig. Binding of these peptides to GRP78 was confirmed using an oriented immobilization technique for the Biacore system. We further examined the ability of the peptides to target cancer cells through in vitro binding studies with cell lines and clinical cancer specimens, and in vivo tumor imaging and targeted chemotherapeutic studies. MicroSPECT/CT imaging revealed significantly greater uptake of (188)Re-liposomes linked to these peptides as compared with non-targeting (188)Re-liposomes. Conjugation with these peptides also significantly increased the therapeutic efficacy of Lipo-Dox. Notably, peptide-conjugated Lipo-Dox significantly reduced stem-cell subpopulation in xenografts of breast cancer. The structure-based optimization strategy for peptides described here may be useful for developing peptide drugs for cancer imaging and therapy. PMID:27088408

  18. Efficacy of whey protein gel networks as potential viability-enhancing scaffolds for cell immobilization of Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Doherty, S B; Gee, V L; Ross, R P; Stanton, C; Fitzgerald, G F; Brodkorb, A

    2010-03-01

    This study investigated cell immobilization of Lactobacillus rhamnosus GG in three separate protein products: native, denatured and hydrolysed whey protein isolate (WPI). Treatments were assessed for their ability to enhance probiotic survival during storage, heat stress and ex vivo gastric incubation. Spatial distribution of probiotic cells within immobilized treatments was evaluated by atomic force and confocal scanning laser microscopy, while cell viability was enumerated by plate count and flow cytometry (FACS). Microscopic analysis of denatured treatments revealed an oasis of immobilized cells, phase-separated from the surrounding protein matrix; an environmental characteristic analogous to hydrolysed networks. Cell immobilization in hydrolysed and denatured WPI enhanced survival by 6.1+/-0.1 and 5.8+/-0.1 log10 cycles, respectively, following 14 day storage at 37 degrees C and both treatments generated thermal protection at 57 degrees C (7.3+/-0.1 and 6.5+/-0.1 log(10) cfu/ml). Furthermore, denatured WPI enhanced probiotic protection (8.9+/-0.2 log(10) cfu/ml) following 3h gastric incubation at 37 degrees C. In conclusion, hydrolysed or denatured WPI were the most suitable matrices for cell immobilization, while native protein provided the weakest safeguard against thermal and acid stress, thus making it possible to envision whey protein gel networks as protective substrates for cell immobilization applications. PMID:20045713

  19. N-bromotaurine surrogates for loss of antiproliferative response and enhances cisplatin efficacy in cancer cells with impaired glucocorticoid receptor.

    Science.gov (United States)

    Logotheti, Stella; Khoury, Nikolas; Vlahopoulos, Spiros A; Skourti, Elena; Papaevangeliou, Dimitra; Liloglou, Triantafyllos; Gorgoulis, Vassilis; Budunova, Irina; Kyriakopoulos, Anthony M; Zoumpourlis, Vassilis

    2016-07-01

    Glucocorticoids (GCs) are frequently used in anticancer combination regimens; however, their continuous use adds selective pressure on cancer cells to develop GC-resistance via impairment of the glucocorticoid receptor (GR), therefore creating a need for GC-alternatives. Based on the drug repurposing approach and the commonalities between inflammation and neoplasia, drugs that are either in late-stage clinical trials and/or already marketed for GC-refractory inflammatory diseases could be evaluated as GC-substitutes in the context of cancer. Advantageously, unlike new molecular entities currently being de novo developed to restore GC-responsiveness of cancer cells, such drugs have documented safety and efficacy profile, which overall simplifies their introduction in clinical cancer trials. In this study, we estimated the potential of a well-established, multistage, cell line-based, mouse skin carcinogenesis model to be exploited as an initial screening tool for unveiling covert GC-substitutes. First, we categorized the cell lines of this model to GC-sensitive and GC-resistant, in correlation with their corresponding GR status, localization, and functionality. We found that GC-resistance starts in papilloma stages, due to a dysfunctional GR, which is overexpressed, DNA binding-competent, but transactivation-incompetent in papilloma, squamous, and spindle stages of the model. Then, aided by this tool, we evaluated the ability of N-bromotaurine, a naturally occurring, small-molecule, nonsteroid anti-inflammatory drug which is under consideration for use interchangeably/in replacement to GCs in skin inflammations, to restore antiproliferative response of GC-resistant cancer cells. Unlike GCs, N-bromotaurine inhibited cell-cycle progression in GC-resistant cancer cells and efficiently synergized with cisplatin, thus indicating a potential to be exploited instead of GCs against cancer. PMID:27063960

  20. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  1. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    Directory of Open Access Journals (Sweden)

    Hutzen Brian

    2012-11-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS, has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. Methods We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease or right lateral ventricle (disseminated disease and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. Results MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. Conclusions These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for

  2. Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

    International Nuclear Information System (INIS)

    Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV) can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS), has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease) or right lateral ventricle (disseminated disease) and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for the treatment of medulloblastoma

  3. Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

    International Nuclear Information System (INIS)

    The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

  4. The efficacy of the enhanced Aussie Optimism Positive Thinking Skills Program in improving social and emotional learning in middle childhood

    OpenAIRE

    SharinazHassan

    2014-01-01

    The aim of the current study was to investigate the effects of the modified and enhanced Aussie Optimism Positive Thinking Skills Program (AO-PTS) on Year 4 and 5 children’s social and emotional learning (SEL) skills. AO-PTS is a universal-school based program that is implemented by class teachers as part of regular school curricula and was developed for the prevention of depression and anxiety. The study comprised a total of 683 Year 4 and 5 students from 10 private primary schools in Wester...

  5. Efficacy of 'breath holding at ease' during CT pulmonary angiography in the improvement of contrast enhancement in pulmonary arteries

    International Nuclear Information System (INIS)

    The aim of this study is to assess whether breath-hold at ease by patients during the CT pulmonary angiography (CTPA) will improve contrast enhancement in pulmonary arteries. Retrospective review was conducted on 51 consecutive CTPA studies undertaken in the traditional method of patients taking deep inspiration and breath-hold immediately prior to scanning, and subsequently 75 consecutive CTPA studies with patients breathing-holding at ease immediately prior to and during the scanning. Attenuation values in pulmonary arteries of different anatomical levels in both groups were measured in Hounsfield unit (HU). Results were compared between the two groups. The mean attenuation value in pulmonary arteries including pulmonary trunk, main and proximal pulmonary arteries calculated in HU in the 'deep inspiration and breath-hold' group was 327 HU (95% confidence interval: 315 to 339 HU). The mean attenuation value in pulmonary arteries in the 'breath hold at ease' group was calculated to be 390 HU (95% confidence interval: 381 to 399 HU); that is, an overall 17.95% increase (P-value<0.0001) in attenuation value in this group. By asking patients to breath-hold at ease instead of taking deep inspiration and breath hold prior to CTPA scan can effectively improve contrast enhancement in pulmonary arteries, therefore producing a higher-quality CT pulmonary angiography scan.

  6. The Efficacy of the Enhanced Aussie Optimism Positive Thinking Skills Program in Improving Social and Emotional Learning in Middle Childhood

    Directory of Open Access Journals (Sweden)

    Jacqueline D Myles-Pallister

    2014-08-01

    Full Text Available The aim of the current study was to investigate the effects of the modified and enhanced Aussie Optimism Positive Thinking Skills Program (AO-PTS on Year 4 and 5 children’s social and emotional learning (SEL skills. AO-PTS is a universal-school based program that is implemented by class teachers as part of regular school curricula and was developed for the prevention of depression and anxiety. The study comprised a total of 683 Year 4 and 5 students from 10 private primary schools in Western Australia. Students were assessed on two subscales of emotional attribution at school whilst parents reported on their children’s externalizing and internalizing problems outside of school and at home. Two analyses were conducted: seven intervention schools were assessed at pre- and post-test (Analysis 1 and pre-post change in three intervention schools were compared to pre-post change in three matched control schools (Analysis 2. Results from Analysis 1 showed that the intervention children had increased in their overall emotional attribution accuracy and decreased in total difficulties and hyperactivity; Results from Analysis 2 revealed no intervention effect on emotional attribution accuracy or internalizing or externalizing problems. These findings suggest that the enhanced AO-PTS’s effects on SEL were not evident in the short-term period after intervention. The non-significant findings and future directions for AO-PTS research and program modification were discussed.

  7. High therapeutic efficacy of Cathelicidin-WA against postweaning diarrhea via inhibiting inflammation and enhancing epithelial barrier in the intestine

    Science.gov (United States)

    Yi, Hongbo; Zhang, Lin; Gan, Zhenshun; Xiong, Haitao; Yu, Caihua; Du, Huahua; Wang, Yizhen

    2016-01-01

    Diarrhea is a leading cause of death among young mammals, especially during weaning. Here, we investigated the effects of Cathelicidin-WA (CWA) on diarrhea, intestinal morphology, inflammatory responses, epithelial barrier and microbiota in the intestine of young mammals during weaning. Piglets with clinical diarrhea were selected and treated with saline (control), CWA or enrofloxacin (Enro) for 4 days. Both CWA and Enro effectively attenuated diarrhea. Compared with the control, CWA decreased IL-6, IL-8 and IL-22 levels and reduced neutrophil infiltration into the jejunum. CWA inhibited inflammation by down-regulating the TLR4-, MyD88- and NF-κB-dependent pathways. Additionally, CWA improved intestinal morphology by increasing villus and microvillus heights and enhancing intestinal barrier function by increasing tight junction (TJ) protein expression and augmenting wound-healing ability in intestinal epithelial cells. CWA also improved microbiota composition and increased short-chain fatty acid (SCFA) levels in feces. By contrast, Enro not only disrupted the intestinal barrier but also negatively affected microbiota composition and SCFA levels in the intestine. In conclusion, CWA effectively attenuated inflammation, enhanced intestinal barrier function, and improved microbiota composition in the intestines of weaned piglets. These results suggest that CWA could be an effective and safe therapy for diarrhea or other intestinal diseases in young mammals. PMID:27181680

  8. Enhanced Protective Efficacy of H5 Subtype Influenza Vaccine with Modification of the Multibasic Cleavage Site of Hemagglutinin in Retroviral Pseudotypes

    Institute of Scientific and Technical Information of China (English)

    Ling Tao; JianJun Chen; Jin Meng; Yao Chen; Hongxia Li; Yan Liu; Zhenhua Zheng

    2013-01-01

    Traditionally,the multibasic cleavage site (MBCS) of surface protein H5-hemagglutinin (HA) is converted to a monobasic one so as to weaken the virulence of recombinant H5N1 influenza viruses and to produce inactivated and live attenuated vaccines.Whether such modification benefits new candidate vaccines has not been adequately investigated.We previously used retroviral vectors to generate wtH5N1 pseudotypes containing the wild-type HA (wtH5) from A/swine/Anhui/ca/2004 (H5N1) virus.Here,we generated mtH5N1 pseudotypes,which contained a mutant-type HA (mtH5) with a modified monobasic cleavage site.Groups of mice were subcutaneously injected with the two types of influenza pseudotypes.Compared to the group immunized with wtH5N1 pseudotypes,the inoculation of mtH5N1 pseudotypes induced significantly higher levels of HA specific IgG and IFN-γ in immunized mice,and enhanced protection against the challenge of mouse-adapted avian influenza virus A/Chicken/Henan/12/2004 (H5N1).This study suggests modification of the H5-hemagglutinin MBCS in retroviral pseudotypes enhances protection efficacy in mice and this information may be helpful for development of vaccines from mammalian cells to fight against H5N1 influenza viruses.

  9. Triterpene-loaded microemulsion using Coix lacryma-jobi seed extract as oil phase for enhanced antitumor efficacy: preparation and in vivo evaluation.

    Science.gov (United States)

    Qu, Ding; He, Junjie; Liu, Congyan; Zhou, Jing; Chen, Yan

    2014-01-01

    Ganoderma lucidum triterpene-loaded microemulsions (TMEs) using Coix lacryma-jobi (adlay) seed oil as oil phase were prepared, characterized, and evaluated for enhanced antitumor activity. Ternary phase diagrams for the TMEs were constructed and the optimal preparation was developed. Transmission electron microscopy and dynamic light scattering showed that this formulation had a well defined spherical shape, a homogeneous distribution, a small size, and a narrow polydispersity index. The drug-loading rate was determined to be 9.87% by ultraviolet spectrophotometry, and acceptable stability under various stimulations in vitro was confirmed. Importantly, the TME formulation showed a significantly greater antiproliferative effect towards human lung carcinoma (A549) cells and murine lung tumor (Lewis) cells in comparison with suspension formulations containing triterpene and adlay seed oil as a positive control. The half-maximal inhibitory concentration of the TMEs was about 0.62 mg crude drug per mL, being 2.5-fold improved relative to that of the corresponding suspension formulation, but no significant cytotoxicity was observed for the bare microemulsion in A549 cells and Lewis cells. In vivo, the TME formulation showed markedly enhanced antitumor efficacy in a xenograft model of Lewis lung cancer after intragastric administration. Compared with cyclophosphamide, the TME formulation showed similar antitumor activity but less general toxicity. These results indicate the feasibility of using a microemulsion to increase the solubility of triterpene and adlay. TMEs hold promise as an efficient drug delivery system for the treatment of lung cancer. PMID:24379669

  10. Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic toll-like receptor ligands

    Directory of Open Access Journals (Sweden)

    Kornbluth Richard S

    2009-08-01

    Full Text Available Abstract Background Targeting of protein antigens to dendritic cells (DC via the DEC205 receptor enhances presentation of antigen-derived peptides on MHC-I and MHC-II molecules and, in the presence of costimulatory signals, antigen-specific immune responses. The immunogenicity and efficacy of DNA vaccination can also be enhanced by fusing the encoded antigen to single chain antibodies directed against DEC205. To further improve this strategy, we evaluated different toll-like receptor ligands (TLR and CD40 ligands (CD40L as adjuvants for DNA vaccines encoding a DEC205-single-chain antibody fused to the ovalbumin model antigen or HIV-1 Gag and assessed the priming efficacy of DNA in a DNA prime adenoviral vector boost immunization regimen. Results Mice were primed with the adjuvanted DEC-205 targeted DNA vaccines and boosted with adenoviral vectors encoding the same antigens. CD8+ T cell responses were determined after the adenoviral booster immunization, to determine how well the different DNA immunization regimens prime for the adenoviral boost. In the absence of adjuvants, targeting of DNA-encoded ovalbumin to DCs suppressed CD8+ T-cell responses after the adenoviral booster immunization. CD8+ T-cell responses to the DEC205 targeted DNA vaccines increased only slightly by adding either the TLR-9 ligand CpG, the TLR-3 ligand Poly I:C, or CD40 ligand expression plasmids. However, the combination of both TLR-ligands led to a strong enhancement of CD8+ T-cell responses compared to a non-targeted DNA vaccine. This finding was confirmed using HIV Gag as antigen. Conclusion Although DNA prime adenoviral vector boost immunizations belong to the strongest inducers of cytotoxic T cell responses in different animal models and humans, the CD8+ T cell responses can be further improved by targeting the DNA encoded antigen to DEC205 in the presence of synergistic TLR ligands CpG and Poly I:C.

  11. Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.

    Directory of Open Access Journals (Sweden)

    Marwan Moussa

    Full Text Available PURPOSE: To determine the effect of different drug-loaded nanocarriers (micelles and liposomes on delivery and treatment efficacy for radiofrequency ablation (RFA combined with nanodrugs. MATERIALS/METHODS: Fischer 344 rats were used (n = 196. First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm, with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm or liposomal (100 nm preparations of doxorubicin (Dox; targeting HIF-1α or quercetin (Qu; targeting HSP70. Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg i.v., 15 min post-RFA, and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg i.v.. Tumor coagulation and HIF-1α or HSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr. RESULTS: Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm and liver (100 nm (p<0.05. Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05. RFA/Mic-Dox had greater early (4 hr intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24-72 hr post-RFA (p<0.04. No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03. CONCLUSION: With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug

  12. Antitumor Efficacy of Anti-GD2 IgG1 Is Enhanced by Fc Glyco-Engineering.

    Science.gov (United States)

    Xu, Hong; Guo, Hongfen; Cheung, Irene Y; Cheung, Nai-Kong V

    2016-07-01

    The affinity of therapeutic antibodies for Fcγ receptors (FcγRs) strongly influences their antitumor potency. To generate antibodies with optimal binding and immunologic efficacy, we compared the affinities of different versions of an IgG1 Fc region that had an altered peptide backbone, altered glycans, or both. To produce IgG1 with glycans that lacked α1,6-fucose, we used CHO cells that were deficient in the enzyme UDP-N-acetylglucosamine: α-3-d-mannoside-β-1,2-N-acetylglucosaminyltransferase I (GnT1), encoded by the MGAT1 gene. Mature N-linked glycans require this enzyme, and without it, CHO cells synthesize antibodies carrying only Man5-GlcNAc2, which were more effective in antibody-dependent cell-mediated cytotoxicity (ADCC). Our engineered IgG1, hu3F8-IgG1, is specific for GD2, a neuroendocrine tumor ganglioside. Its peptide mutant is IgG1-DEL (S239D/I332E/A330L), both produced in wild-type CHO cells. When produced in GnT1-deficient CHO cells, we refer to them as IgG1n and IgG1n-DEL, respectively. Affinities for human FcγRs were measured using Biacore T-100 (on CD16 and CD32 polymorphic alleles), their immunologic properties compared for ADCC and complement-mediated cytotoxicity (CMC) in vitro, and pharmacokinetics and antitumor effects were compared in vivo in humanized mice. IgG1n and IgG1n-DEL contained only mannose and acetylglucosamine and had preferential affinity for activating CD16s, over inhibitory CD32B, receptors. In vivo, the antitumor effects of IgG1, IgG1-DEL, and IgG1n-DEL were similar but modest, whereas IgG1n was significantly more effective (P < 0.05). Thus, IgG1n antibodies produced in GnT1-deficient CHO cells may have potential as improved anticancer therapeutics. Cancer Immunol Res; 4(7); 631-8. ©2016 AACR. PMID:27197064

  13. Lymphotactin enhances the in-vitro immune efficacy of dendritoma formed by dendritic cells and mouse hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    张浩; 蒋国平; 郑树森; 吴丽花; 朱峰; 杨振林

    2004-01-01

    Objective: To investigate the in-vitro antitumor immune responses of dendritoma formed by mouse hepatocellular carcinoma (HCC) cells and lymphotactin (Lptn) gene modified dendritic cells (DCs). Method: DCs prepared from mouse bone marrow were genetically modified by lymphotactin adenovirus, and fused with H22 cells by polyethylene glycol (PEG). RT-PCR and ELISA were employed to identify lymphotactin expression at mRNA and protein level. Cell phenotypes and fusion efficiency was detected by FACS. The stimulatory effect of DC on T cells was detected by mixed lymphocyte reaction. The cytotoxicity activity against H22 cells was assayed by LDH method. Results: Lymphotactin could be efficiently expressed by DCLptn/H22 hybridoma. DCLptn/H22 cells could induce potent T cell proliferation effect and generate strong cytotoxic T lymphocyte (CTL) reaction against allogenic H22 cells. Conclusion: Lymphotactin genetic modification could enhance the in vitro immune activity of the dendritoma.

  14. Journey of Mesenchymal Stem Cells for Homing: Strategies to Enhance Efficacy and Safety of Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Sung Keun Kang

    2012-01-01

    Full Text Available Human mesenchymal stem cells (MSCs communicate with other cells in the human body and appear to “home” to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and the in vivo environment facilitate and are required for the migration of MSCs to the site of insult or injury in vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.

  15. Cell Permeating Nano-Complexes of Amphiphilic Polyelectrolytes Enhance Solubility, Stability, and Anti-Cancer Efficacy of Curcumin.

    Science.gov (United States)

    Fatima, Munazza T; Chanchal, Abhishek; Yavvari, Prabhu S; Bhagat, Somnath D; Gujrati, Mansi; Mishra, Ram K; Srivastava, Aasheesh

    2016-07-11

    Many hydrophobic drugs encounter severe bioavailability issues owing to their low aqueous solubility and limited cellular uptake. We have designed a series of amphiphilic polyaspartamide polyelectrolytes (PEs) that solubilize such hydrophobic drugs in aqueous medium and enhance their cellular uptake. These PEs were synthesized through controlled (∼20 mol %) derivatization of polysuccinimide (PSI) precursor polymer with hydrophobic amines (of varying alkyl chain lengths, viz. hexyl, octyl, dodecyl, and oleyl), while the remaining succinimide residues of PSI were opened using a protonable and hydrophilic amine, 2-(2-amino-ethyl amino) ethanol (AE). Curcumin (Cur) was employed as a representative hydrophobic drug to explore the drug-delivery potential of the resulting PEs. Unprecedented enhancement in the aqueous solubility of Cur was achieved by employing these PEs through a rather simple protocol. In the case of PEs containing oleyl/dodecyl residues, up to >65000× increment in the solubility of Cur in aqueous medium could be achieved without requiring any organic solvent at all. The resulting suspensions were physically and chemically stable for at least 2 weeks. Stable nanosized polyelectrolyte complexes (PECs) with average hydrodynamic diameters (DH) of 150-170 nm (without Cur) and 220-270 nm (after Cur loading) were obtained by using submolar sodium polyaspartate (SPA) counter polyelectrolyte. The zeta potential of these PECs ranged from +36 to +43 mV. The PEC-formation significantly improved the cytocompatibility of the PEs while affording reconstitutable nanoformulations having up to 40 wt % drug-loading. The Cur-loaded PECs were readily internalized by mammalian cells (HEK-293T, MDA-MB-231, and U2OS), majorly through clathrin-mediated endocytosis (CME). Cellular uptake of Cur was directly correlated with the length of the alkyl chain present in the PECs. Further, the PECs significantly improved nuclear transport of Cur in cancer cells, resulting in their

  16. Enhanced efficacy of synergistic combinations of antimicrobial peptides with caspofungin versus Candida albicans in insect and murine models of systemic infection.

    Science.gov (United States)

    MacCallum, D M; Desbois, A P; Coote, P J

    2013-08-01

    The objective of this study was to determine whether combinations of antimicrobial peptides (AMPs) with caspofungin display enhanced antifungal activity versus Candida albicans in vitro and in vivo. Three conventional AMPs that satisfied criteria favouring their potential development as novel antifungals were selected for investigation. Colistin sulphate was also included as a cyclic peptide antibiotic used in the clinic. Minimum inhibitory concentrations (MICs) were determined for each antifungal agent and checkerboard assays were used to determine fractional inhibitory concentration index (FICI) values for dual combinations of AMPs or colistin with caspofungin. Viability assays were performed for the same combinations in order to investigate fungicidal interactions. Synergistic antifungal combinations were then tested for efficacy in vivo and compared to monotherapies in wax moth larva and murine models of systemic C. albicans infection. In combination with caspofungin, each of the AMPs [hMUC7-12, DsS3(1-16), hLF(1-11)] and colistin were synergistic and candidacidal in vitro. The treatment of infected wax moth larvae with combinations of caspofungin with hMUC7-12, DsS3(1-16) or colistin resulted in significant enhancements in survival compared to treatment with monotherapies. Notably, the treatment of C. albicans-infected mice with a combination of caspofungin and DsS3(1-16) resulted in the enhancement of survival compared to groups treated with just the individual agents. This study demonstrates that combination therapies containing caspofungin and AMPs or colistin merit further development as potential novel treatments for C. albicans infections. PMID:23572153

  17. Concomitant administration of Mycobacterium bovis BCG with the meningococcal C conjugate vaccine to neonatal mice enhances antibody response and protective efficacy.

    Science.gov (United States)

    Brynjolfsson, Siggeir F; Bjarnarson, Stefania P; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif

    2011-11-01

    Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM(197), in mice primed as neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1 and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.) with MenC-CRM(197). BCG was administered concomitantly, a day or a week before MenC-CRM(197). An adjuvant effect of BCG was observed only when it was given concomitantly with MenC-CRM(197), with increased IgG response (P = 0.002) and SBA (8-fold) after a second immunization with MenC-CRM(197) without BCG, indicating increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC-CRM(197) together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced compared to MenC-CRM(197) alone (P = 0.0015). Sixteen days after the second immunization with MenC-CRM(197), increased IgG (P CRM(197) plus BCG showed affinity maturation and detectable SBA (SBA > 128). Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other conjugates) may benefit from concomitant administration of BCG in the neonatal period to accelerate and enhance production of protective antibodies, compared to the current infant administration of conjugate which follows BCG vaccination at birth. PMID:21900528

  18. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

    Science.gov (United States)

    Arciero, Paul J; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J; Astrup, Arne

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p 50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet. PMID:27483317

  19. Lipopolysaccharide preconditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Wang Zhaojun

    2009-08-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs-based regenerative therapy is currently regarded as an alternative approach to salvage the acute myocardial infarcted hearts. However, the efficiency of MSCs transplantation is limited by lower survival rate of engrafted MSCs. In previous study, we found that 1.0 μg/ml Lipopolysaccharide (LPS could protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned MSCs with 1.0 μg/ml LPS, then transplanted MSCs into ischemic myocardium, and observed the survival and cardiac protective capacity of MSCs in a rat model of acute myocardial infarction. Furthermore, we tried to explore the underlying mechanisms and the role of Toll-like receptor-4 (TLR4 in the signal pathway of LPS-induced cardiac protection. Methods and results Acute myocardial infarction model was developed by left anterior descending coronary artery ligation. 60 rats were divided into 4 groups randomly and given an intramyocardial injection of one of the following treatments: 30 μl PBS (control group, 3 × 106 wild MSCs/30 μl (wMSCs group, 3 × 106 LPS-preconditioned wild MSCs/30 μl (LPS-wMSCs group, or 3 × 106 LPS-preconditioned TLR4 gene deleted MSCs/30 μl (LPS-tMSCs group. After 3 weeks, LPS-preconditioned wild MSCs transplantation ameliorated cardiac function and reduced fibrosis of infarcted myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and apoptosis of myocardium was reduced in infarcted heart. Expression of vascular endothelial growth factor (VEGF and phospho-Akt was increased in the infarcted myocardium after transplantation of LPS-preconditioned MSCs. Conclusion LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs

  20. Daurinol Enhances the Efficacy of Radiotherapy in Lung Cancer via Suppression of Aurora Kinase A/B Expression.

    Science.gov (United States)

    Woo, Jong Kyu; Kang, Ju-Hee; Shin, DongYun; Park, Seong-Hyeok; Kang, Kyungsu; Nho, Chu Won; Seong, Je Kyung; Lee, Sang-Jin; Oh, Seung Hyun

    2015-07-01

    The aurora kinases constitute one family of serine/threonine kinases whose activity is essential for mitotic progression. The aurora kinases are frequently upregulated in human cancers and are associated with sensitivity to chemotherapy in certain ones. In the present study, we investigated whether aurora kinases could be a target to overcome radioresistance or enhance the radiosensitivity of lung cancer. For that purpose, we determined the therapeutic potential of daurinol, an investigational topoisomerase inhibitor, alone and in combination with radiation, by observing its effect on aurora kinases. Daurinol decreased cell viability and proliferation in human colon and lung cancer cells. Gene expression in daurinol-treated human colon cancer cells was evaluated using RNA microarray. The mRNA expression of 18 genes involved in the mitotic spindle check point, including aurora kinase A (AURKA) and aurora kinase B (AURKB), was decreased in daurinol-treated human colon cancer cells as compared with vehicle-treated cells. As expected, radiation increased expression levels of AURKA and AURKB. This increase was effectively attenuated by siRNAs against AURKA and AURKB, which suppressed cell growth and increased apoptosis under radiation. Furthermore, the expression of AURKA and AURKB was suppressed by daurinol in the presence or absence of radiation in colon and lung cancer cells. Daurinol alone or in combination with radiation decreased lung cancer growth in xenograft mouse models. Our data clearly confirm the antitumor and radiosensitizing activity of daurinol in human lung cancer cells through the inhibition of AURKA and AURKB. PMID:25882311

  1. Encapsulated paclitaxel nanoparticles exhibit enhanced anti-tumor efficacy in A549 non-small lung cancer cells.

    Science.gov (United States)

    Huang, Guojin; Zang, Bao; Wang, Xiaowei; Liu, Gang; Zhao, Jianqiang

    2015-12-01

    In the present study, paclitaxel (PTX) were encapsulated with polyethylene glycol (PEG)-polylactide (PLA)/D-α tocopheryl polyethylene glycol 1000 succinate (TPGS) (PEG-PLA/TPGS) and the enhanced anti-tumor activity of this PTX mixed micelles (PTX-MM) was evaluated in lung cancer cells. The PTX-MM prepared by a solvent evaporation method was demonstrated to have high drug-loading efficiency (23.2%), high encapsulation efficiency (76.4%), and small size (59 nm). In vitro release assay showed the slow release behavior of PTX-MM, suggesting the good stability of the PTX-MM essential for long circulation time. In vitro kinetics assay demonstrated that PTX-MM could promote absorption and increase relative bioavailability. The anti-cancer efficiency of PTX-MM was also examined by both in vitro and in vivo studies. PTX-MM exhibits obvious cytotoxicity against lung cancer cells with much lower IC50 value when compared with commercial formulated PTX or PTX + TPGS. The xenograft tumor model studies on nude mice indicated that PTX-MM inhibits tumor growth more effectively than other formulations. It was also found that most of mixed micelles were integral in tumor site to exhibit anti-cancer activity. Our results suggested that the use of PTX-MM as an anti-cancer drug may be an effective approach to treat lung cancer. PMID:26525950

  2. Immune enhancement by novel vaccine adjuvants in autoimmune-prone NZB/W F1 mice: relative efficacy and safety

    Directory of Open Access Journals (Sweden)

    Ghosh Swapan K

    2011-10-01

    Full Text Available Abstract Background Vaccines have profoundly impacted global health although concerns persist about their potential role in autoimmune or other adverse reactions. To address these concerns, vaccine components like immunogens and adjuvants require critical evaluation not only in healthy subjects but also in those genetically averse to vaccine constituents. Evaluation in autoimmune-prone animal models of adjuvants is therefore important in vaccine development. The objective here was to assess the effectiveness of experimental adjuvants: two phytol-derived immunostimulants PHIS-01 (phytanol and PHIS-03 (phytanyl mannose, and a new commercial adjuvant from porcine small intestinal submucosa (SIS-H, relative to a standard adjuvant alum. Phytol derivatives are hydrophobic, oil-in water diterpenoids, while alum is hydrophilic, and SIS is essentially a biodegradable and collagenous protein cocktail derived from extracellular matrices. Results We studied phthalate -specific and cross-reactive anti-DNA antibody responses, and parameters associated with the onset of autoimmune disorders. We determined antibody isotype and cytokine/chemokine milieu induced by the above experimental adjuvants relative to alum. Our results indicated that the phytol-derived adjuvant PHIS-01 exceeded alum in enhancing anti-phthalate antibody without much cross reactivity with ds-DNA. Relatively, SIS and PHIS-03 proved less robust, but they were also less inflammatory. Interestingly, these adjuvants facilitated isotype switching of anti-hapten, but not of anti-DNA response. The current study reaffirms our earlier reports on adjuvanticity of phytol compounds and SIS-H in non autoimmune-prone BALB/c and C57BL/6 mice. These adjuvants are as effective as alum also in autoimmune-prone NZB/WF1 mice, and they have little deleterious effects. Conclusion Although all adjuvants tested impacted cytokine/chemokine milieu in favor of Th1/Th2 balance, the phytol compounds fared better in

  3. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

    Science.gov (United States)

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich’s ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

  4. Triterpene-loaded microemulsion using Coix lacryma-jobi seed extract as oil phase for enhanced antitumor efficacy: preparation and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Qu D

    2013-12-01

    Full Text Available Ding Qu, Junjie He, Congyan Liu, Jing Zhou, Yan ChenKey Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, People’s Republic of ChinaAbstract: Ganoderma lucidum triterpene-loaded microemulsions (TMEs using Coix lacryma-jobi (adlay seed oil as oil phase were prepared, characterized, and evaluated for enhanced antitumor activity. Ternary phase diagrams for the TMEs were constructed and the optimal preparation was developed. Transmission electron microscopy and dynamic light scattering showed that this formulation had a well defined spherical shape, a homogeneous distribution, a small size, and a narrow polydispersity index. The drug-loading rate was determined to be 9.87% by ultraviolet spectrophotometry, and acceptable stability under various stimulations in vitro was confirmed. Importantly, the TME formulation showed a significantly greater antiproliferative effect towards human lung carcinoma (A549 cells and murine lung tumor (Lewis cells in comparison with suspension formulations containing triterpene and adlay seed oil as a positive control. The half-maximal inhibitory concentration of the TMEs was about 0.62 mg crude drug per mL, being 2.5-fold improved relative to that of the corresponding suspension formulation, but no significant cytotoxicity was observed for the bare microemulsion in A549 cells and Lewis cells. In vivo, the TME formulation showed markedly enhanced antitumor efficacy in a xenograft model of Lewis lung cancer after intragastric administration. Compared with cyclophosphamide, the TME formulation showed similar antitumor activity but less general toxicity. These results indicate the feasibility of using a microemulsion to increase the solubility of triterpene and adlay. TMEs hold promise as an efficient drug delivery system for the treatment of lung cancer.Keywords: microemulsion, Ganoderma lucidum, triterpene, adlay seed oil, lung cancer

  5. Granulocyte-macrophage colony-stimulating factor DNA prime-protein boost strategy to enhance efficacy of a recombinant pertussis DNA vaccine

    Institute of Scientific and Technical Information of China (English)

    Qing-tian LI; Yong-zhang ZHU; Jia-you CHU; Ke DONG; Ping HE; Chun-yan FENG; Bao-yu HU; Shu-min ZHANG; Xiao-kui GUO

    2006-01-01

    Aim: To investigate a new strategy to enhance the efficacy of a recombinant pertussis DNA vaccine. The strategy is co-injection with cytokine plasmids as prime, and boosted with purified homologous proteins. Method: A recombinant pertussis DNA vaccine containing the pertussis toxin subunit 1 (PTS1), fragments of the filamentous hemagglutinin (FHA) gene and pertactin (PRN) gene encoding filamentous hemagglutinin and pertactin were constructed. Balb/c mice were immunized with several DNA vaccines and antigen-specific antibodies anti-PTSl, anti-PRN, anti-FHA, cytokines interleukin (IL)-10, IL-4, IFN-γ, TNF-oc, and spleno-cyte-proliferation assay were used to describe immune responses. Results: The recombinant DNA vaccine could elicit similar immune responses in mice as that of separate plasmids encoding the 3 fragments, respectively. Mice immunized with DNA and boosted with the corresponding protein elicited more antibodies than those that received DNA as boost. In particular, when the mice were co-immunized with murine granulocyte-macrophage colony-stimulating factor plasmids and boosted with proteins, all 4 cytokines and the 3 antigen-specific antibodies were significantly increased compared to the pVAXl group. Anti-PTSl, anti-FHA, IL-4 and TNF-α elicited in the colony stimulating factor (CSF) prime-protein boost group showed significant increase compared to all the other groups. Conclusion: This prime and boost strategy has proven to be very useful in improving the immunogenicity of DNA vaccines against pertussis.

  6. Regulation of Mucin 1 and multidrug resistance protein 1 by honokiol enhances the efficacy of doxorubicin-mediated growth suppression in mammary carcinoma cells.

    Science.gov (United States)

    Thulasiraman, Padmamalini; Johnson, Andrea Butts

    2016-08-01

    Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate. The objective of this study was to understand the relationship between MUC1 and MRP1 using natural phenolic compound isolated from Magnolia grandiflora, honokiol, in mammary carcinoma cells. We provide evidence that honokiol suppresses the expression level of MUC1 and MRP1 in mammary carcinoma cells. In a time-dependent manner, honokiol-mediated reduction of MUC1 is followed by a reduction of MRP1 expression in the breast cancer cells. Additionally, silencing MUC1 suppresses the expression level of MRP1 and enhances the efficacy of doxorubicin, an MRP1 substrate. Taken together, these findings suggest MUC1 regulates the expression of MRP1 and provides a direct link between cancer progression and chemoresistance in mammary carcinoma cells. PMID:27221150

  7. Enhanced efficacy of combined {sup 213}Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Gilbertz, Klaus-Peter [German Armed Forces, Institute of Radiobiology, Munich (Germany); Baumgart, Anja [Technische Universitaet Muenchen, III. Medical Department, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K. [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-12-15

    Targeted therapy with {alpha}-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the {alpha}-emitter {sup 213}Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined {sup 213}Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with {sup 213}Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined {sup 213}Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with {sup 213}Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 {mu}g) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with {sup 213}Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either {sup 213}Bi-DTPA-F3 or paclitaxel alone. Combined treatment with {sup 213}Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  8. Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    International Nuclear Information System (INIS)

    Targeted therapy with α-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the α-emitter 213Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined 213Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either 213Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with 213Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined 213Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either 213Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with 213Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 μg) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with 213Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either 213Bi-DTPA-F3 or paclitaxel alone. Combined treatment with 213Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  9. Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats.

    Science.gov (United States)

    El-Shemi, Adel Galal; Refaat, Bassem; Kensara, Osama Adnan; Mohamed, Amr Mohamed; Idris, Shakir; Ahmad, Jawwad

    2016-06-01

    Colorectal cancer is a common cancer with high mortality rate. Despite being the standard anti-colorectal cancer drug, 5-fluorouracil (5-FU) exhibits only limited therapeutic benefits. Herein, we investigated whether paricalcitol, a synthetic vitamin D analogue with potential antitumor properties, would enhance the chemopreventive efficacy of 5-FU on an intermediate-term (15 weeks) model of colorectal tumors induced by azoxymethane (AOM) in rats. After AOM injection, 5-FU was administered during the 9th and 10th weeks (12 mg/kg/day for 4 days, then 6 mg/kg every other day for another 4 doses), whereas paricalcitol (2.5 μg/kg/day; 3 days/week) was given from the 7th to the 15th week. At week 15, the animals were euthanized and their resected colons were examined macroscopically and microscopically. Quantitative RT-PCR was used to measure the transcription activities of Wnt, β-catenin, DKK-1, CDNK-1A, NF-κB, and COX-2 genes, and ELISA was used to quantify the protein levels of β-catenin, COX-2, HSP90, and VEGF. IHC was additionally used to measure β-catenin, HSP90, and inducible nitric oxide synthase (iNOS). Compared with their individual therapy, combination of 5-FU and paricalcitol showed more significant reducing effect on numbers of grown tumors and large aberrant crypts foci. Mechanistically, paricalcitol and 5-FU had cooperated together to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and HSP-90 more, and to upregulate the expression of antitumorigenesis DKK-1 and CDNK-1A, compared with their monotherapies. Our findings suggest that combined use of paricalcitol with 5-FU exhibits an augmenting chemopreventive effect against colorectal tumors, and might potentially be useful for chemoprevention in colorectal cancer patients. Cancer Prev Res; 9(6); 491-501. ©2016 AACR. PMID:27020656

  10. Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol-poly(ε-caprolactone nanoparticles

    Directory of Open Access Journals (Sweden)

    Liu Q

    2012-01-01

    Full Text Available Qin Liu1*, Ru-Tian Li1*, Han-Qing Qian2, Mi Yang1, Zhen-Shu Zhu2, Wei Wu2, Xiao-Ping Qian1, Li-Xia Yu1, Xi-Qun Jiang2, Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing 210008, China; 2Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering College of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China*These authors contributed equally to this workAbstract: Nanoscale drug carriers have been extensively developed to improve drug therapeutic efficiency. However, delivery of chemotherapeutic agents to tumor tissues and cells has not been favorably managed. In this study, we developed a novel “intelligent” nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol (PEG and poly(ε-caprolactone (PCL-based structure for tumor-targeted docetaxel delivery (DOC-TNPs. The docetaxel-loaded PEG-PCL nanoparticles (DOC-NPs that did not display gelatinase-stimuli behaviors were used as a control. We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01. In vivo biodistribution study demonstrated that targeted DOC-TNPs could accumulate and remain in the tumor regions, whereas non-targeted DOC-NPs rapidly eliminated from the tumor tissues. DOC-TNPs exhibited higher tumor growth suppression than commercialized Taxotere® (docetaxel; Jiangsu Hengrui Medicine Company, Jiangsu, China and DOC-NPs on hepatic H22 tumor model via intravenous administration (P < 0.01. Both in vitro and in vivo experiments suggest that the gelatinase-mediated nanoscale delivery system is promising for improvement of antitumor efficacy in various overexpressed gelatinase cancers.Keywords: drug delivery, stimuli-responsive, gelatinase, antitumor, docetaxel

  11. Chief Joseph Kokanee Enhancement Project; Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at the Grand Coulee Dam Third Powerplant Forebay, 2002-2003 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, R.; McKinstry, C.; Simmons, C. (Pacific Northwest National Laboratory)

    2003-01-01

    Since 1995, the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes) have managed the Chief Joseph Kokanee Enhancement Project as part of the Northwest Power Planning Council (NWPPC) Fish and Wildlife Program. Project objectives have focused on understanding natural production of kokanee (a land-locked sockeye salmon) and other fish stocks in the area above Grand Coulee and Chief Joseph Dams on the Columbia River. A 42-month investigation concluded that entrainment at Grand Coulee Dam ranged from 211,685 to 576,676 fish annually. Further analysis revealed that 85% of the total entrainment occurred at the dam's third powerplant. These numbers represent a significant loss to the tribal fisheries upstream of the dam. In response to a suggestion by the NWPPC Independent Scientific Review Panel, the scope of work for the Chief Joseph Kokanee Enhancement Project was expanded to include a multiyear pilot test of a strobe light system to help mitigate fish entrainment. This report details the work conducted during the second year of the study by researchers of the Colville Confederated Tribes in collaboration with the Pacific Northwest National Laboratory. The 2002 study period extended from May 18 through July 30. The objective of the study was to determine the efficacy of a prototype strobe light system to elicit a negative phototactic response in kokanee and rainbow trout. The prototype system consisted of six strobe lights affixed to an aluminum frame suspended vertically underwater from a barge secured in the center of the entrance to the third powerplant forebay. The lights, controlled by a computer, were aimed to illuminate a specific region directly upstream of the barge. Three light level treatments were used: 6 of 6 lights on, 3 of 6 lights on, and all lights off. These three treatment conditions were applied for an entire 24-hr day and were randomly assigned within a 3-day block throughout the study period. A seven

  12. Reconstituted high density lipoprotein mediated targeted co-delivery of HZ08 and paclitaxel enhances the efficacy of paclitaxel in multidrug-resistant MCF-7 breast cancer cells.

    Science.gov (United States)

    Zhang, Fangrong; Wang, Xiaoyi; Xu, Xiangting; Li, Min; Zhou, Jianping; Wang, Wei

    2016-09-20

    In the past decades, reconstituted high density lipoprotein (rHDL) has been successfully developed as a drug carrier since the enhanced HDL-lipids uptake is demonstrated in several human cancers. In this paper, rHDL, for the first time, was utilized to co-encapsulate two hydrophobic drugs: an anticancer drug, paclitaxel (PTX), and a new reversal agent for P-gp (P-glycoprotein)-mediated multidrug resistance (MDR) of cancer, N-cyano-1-[(3,4-dimethoxyphenyl)methyl]-3,4-dihydro-6,7-dimethoxy-N'-octyl-2(1H)-isoquinoline-carboximidamide (HZ08). We proposed this drug co-delivery strategy to reverse PTX resistance. The study aimed to develop a biomimetic nanovector, reconstituted high density lipoprotein (rHDL), mediating targeted PTX-HZ08 delivery for cancer therapy. Using sodium cholate dialysis method, we successfully formulated dual-agent co-delivering rHDL nanoparticles (PTX-HZ08-rHDL NPs) with a typical spherical morphology, well-distributed size (~100nm), high drug encapsulation efficiency (approximately 90%), sustained drug release properties and exceptional stability even after storage for 1month or incubation in 10% fetal bovine serum (FBS) DMEM for up to 2days. Results demonstrated that PTX-HZ08-rHDL NPs significantly enhanced anticancer efficacy in vitro, including higher cytotoxicity and better ability to induce cell apoptosis against both PTX-sensitive and -resistant MCF-7 human breast cancer cell lines (MCF-7 and MCF-7/PTX cells). Mechanism studies demonstrated that these improvements could be correlated with increased cellular uptake of PTX mediated by scavenger receptor class B type I (SR-BI) as well as prolonged intracellular retention of PTX due to the HZ08 mediated drug-efflux inhibition. In addition, in vivo investigation showed that the PTX-HZ08-rHDL NPs were substantially safer, have higher tumor-targeted capacity and have stronger antitumor activity than the corresponding dosage of paclitaxel injection. These findings suggested that rHDL NPs could

  13. Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in a murine model of human multiple myeloma: molecular targets for cell cycle arrest and apoptosis induction.

    Science.gov (United States)

    Al-Sadoon, Mohamed K; Rabah, Danny M; Badr, Gamal

    2013-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma drugs remains critically important. We recently described a silica nanoparticle-based snake venom delivery model that targets cancer cells, but not normal cells. Using this model, we demonstrated a strong enhancement of the antitumor activity of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast carcinoma cell lines when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we aimed to delineate the in vivo therapeutic efficacy of WEV+NP in an MM-bearing experimental nude mouse model. We found that treatment with WEV+NP or WEV alone significantly inhibited tumor growth compared to treatment with NP or vehicle. WEV+NP- and WEV-treated cancer cells exhibited marked elevations in oxidative stress and robust reductions in the levels of interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEV+NP also decreased the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a greater extent than WEV alone, and WEV+NP subsequently reduced migration in response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6-mediated MM cell proliferation, altered the cell cycle and enhanced the induction of apoptosis of MM cells. In addition, the results of treatment with WEV+NP or WEV alone revealed that the combination of WEV with NP robustly decreased the expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the expression of cyclin B1; altered the mitochondrial membrane potential; increased the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest and apoptosis. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom to fight cancer cells. PMID:23973876

  14. Chief Joseph Kokanee Enhancement Project : Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at Grond Coulee Dam Third Powerplant Forebay.

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, M.A.; McKinstry, C.A.; Simmons, C.S.

    2002-01-01

    Since 1995, the Colville Confederated Tribes have managed the Chief Joseph Kokanee Enhancement Project as part of the Northwest Power Planning Council's (NWPPC) Fish and Wildlife Program. Project objectives have focused on understanding natural production of kokanee (a land-locked sockeye salmon) and other fish stocks in the area above Grand Coulee and Chief Joseph Dams on the Columbia River. A 42-month investigation concluded that entrainment at Grand Coulee Dam ranged from 211,685 to 576,676 fish annually. Further analysis revealed that 85% of the total entrainment occurred at the dam's third powerplant. These numbers represent a significant loss to the tribal fisheries upstream of the dam. In response to a suggestion by the NWPPC's Independent Scientific Review Panel, the scope of work for the Chief Joseph Kokanee Enhancement Project was expanded to include a multiyear pilot test of a strobe light system to help mitigate fish entrainment. This report details the work conducted during the first year of the study by researchers of the Colville Confederated Tribes in collaboration with the Pacific Northwest National Laboratory (PNNL). The objective of the study was to determine the efficacy of a prototype strobe light system to elicit a negative phototactic response in kokanee and rainbow trout. Analysis of the effect of strobe lights on the distribution (numbers) and behavior of kokanee and rainbow trout was based on 51, 683 fish targets detected during the study period (June 30 through August 1, 2001). Study findings include the following: (1) Analysis of the count data indicated that significantly more fish were present when the lights were on compared to off. This was true for both the 24-hr tests as well as the 1-hr tests. Powerplant discharge, distance from lights, and date were significant factors in the analysis. (2) Behavioral results indicated that fish within 14 m of the lights were trying to avoid the lights by swimming across the lighted

  15. Poly(ethylene glycol-block-poly(ε-caprolactone– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

    Directory of Open Access Journals (Sweden)

    He XD

    2015-03-01

    Full Text Available Xiaodan He,1 Li Li,2 Hong Su,1 Dinglun Zhou,3 Hongmei Song,4 Ling Wang,1 Xuehua Jiang1 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China School of Public Health, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4HitGen Ltd., Chengdu, Sichuan, People’s Republic of China Background: Effective anticancer drug delivery to the tumor site without rapid body clearance is a prerequisite for successful chemotherapy. 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-(methoxy[polyethyleneglycol]-2000 (DSPE-PEG2000 has been widely used in the preparation of stealth liposomes. Although PEG chains can efficiently preserve liposomes from rapid clearance by the reticuloendothelial system (RES, its application has been hindered by poor cellular uptake and unsatisfactory therapeutic effect.Methods: To address the dilemma, we presented a facile approach to fabricate novel stealth nanoparticles generated by poly(ethylene glycol-block-poly(ε-caprolactone (PEG-b-PCL, soybean phosphatidylcholine (SPC, and cholesterol, namely LPPs (L represented lipid and PP represented PEG-b-PCL, for the delivery of anticancer drug paclitaxel (PTX. LPPs were prepared using the thin film hydration method. Two PEG-b-PCL polymers with different molecular weights (MW; PEG2000-b-PCL2000, MW: 4,000 Da and PEG5000-b-PCL5000, MW: 10,000 Da were used to fabricate stealth nanoparticles. Conventional PEGylated liposome (LDP2000, L represented lipid and DP2000 represented DSPE-PEG2000 composed of SPC, cholesterol, and DSPE-PEG2000 was used as the control. The physical properties, cellular uptake, endocytosis pathway, cytotoxicity, pharmacokinetics, tumor accumulation, and anticancer efficacy of free PTX, PTX-loaded LPPs, and LDP2000 were systemically investigated after injection into 4T1

  16. Methylprednisolone enhances the efficacy of ondansetron in acute and delayed cisplatin-induced emesis over at least three cycles. Ondansetron Study Group.

    OpenAIRE

    Chevallier, B.; Marty, M.; Paillarse, J. M.

    1994-01-01

    This double-blind multicentre study has been carried out in order to confirm the improvement of ondansetron's antiemetic efficacy when combined with a corticosteroid and to determine whether this increased efficacy is maintained over three chemotherapy courses. One hundred and two patients receiving their first course of cisplatin (50-120 mg m-2)-containing chemotherapy were randomised to receive one of the two following treatments: 8 mg OND i.v. injection and 120 mg MPD i.v. injection before...

  17. Quenching of singlet oxygen by natural and synthetic antioxidants and assessment of electronic UV/Visible absorption spectra for alleviating or enhancing the efficacy of photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Kaneez Fatima

    2016-02-01

    Full Text Available Photodynamic therapy (PDT is one of the methods involved in cancer therapy exploiting singlet oxygen as a weapon to kill cancer cells. Singlet oxygen, a bizarre reactive oxygen species as it is not related to electron transfer to O2 but it is one of the most active intermediate involved in biochemical reactions as it directly reacts with all the major macromolecules like DNA, protein, lipids etc, various photosensitized oxidations and in the photodegradation of dyes and polymers. Recent studies about the usage of antioxidant along with the photo-sensitizer involved in photodynamic therapy have shown concentration- dependent dual behavior like usually it retards the efficacy of PDT but at a higher dose mostly, it actually enhances the damaging effect of PDT. The natural and synthetic antioxidants are being used in our day to day life in order to increase the shelf life of various food ingredients and processed foods. In this paper, we have compared natural and synthetic antioxidants along with the known singlet oxygen quencher (DABCO in order to understand the quenching potential of singlet oxygen (1O2 which is lowest electronically excited state of molecular oxygen. The singlet oxygen can be artificially generated through various methods such as sunlight, phosphate, ozonides, NaOCl and H2O2 etc. We have studied the mechanisms of the few antioxidant effects on the bleaching of RNO linked with the energy decay of 1O2 produced by the Mallet reaction (H2O2+HOCl and #8200; and #8594; and #8200;HCl+H2O+1O2. beta-Carotene, and #945;-Tocopherol, Ascorbic acid and Quercetin exhibited best dose-dependent singlet quenching ranging from 92.3 to 56.5 % at 100 and #956;M among others. Overall singlet oxygen is a major concern of light-related properties so we have analyzed the theoretical aspect of electronic UV/visible absorption spectra of the antioxidants studied through ZINDO CI semi-empirical Hamiltonian method. We have compared only the first singlet

  18. Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhance Transdermal Permeation in Adjuvant-Induced Rheumatoid Arthritis in the Rat.

    Science.gov (United States)

    Liao, Ai-Ho; Chung, Huan-Yu; Chen, Wen-Shiang; Yeh, Ming-Kung

    2016-08-01

    A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 μL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac-carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area. PMID:27181685

  19. Chief Joseph Kokanee Enhancement Project; Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at the Grand Coulee Dam Third Powerplant Forebay, 2003-2004 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, M.; McKinstry, C.; Cook, C.

    2004-01-01

    Since 1995, the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes) have managed the Chief Joseph Kokanee Enhancement Project as part of the Northwest Power Planning Council (NWPPC) Fish and Wildlife Program. Project objectives have focused on understanding natural production of kokanee (a land-locked sockeye salmon) and other fish stocks in the area above Grand Coulee and Chief Joseph Dams on the Columbia River. A 42-month investigation from 1996 to 1999 determined that from 211,685 to 576,676 fish were entrained annually at Grand Coulee Dam. Analysis of the entrainment data found that 85% of the total entrainment occurred at the dam's third powerplant. These numbers represent a significant loss to the tribal fisheries upstream of the dam. In response to a suggestion by the NWPPC Independent Scientific Review Panel, the scope of work for the Chief Joseph Kokanee Enhancement Project was expanded to include a multiyear pilot test of a strobe light system to help mitigate fish entrainment. This report details the work conducted during the third year of the strobe light study by researchers of the Colville Confederated Tribes in collaboration with the Pacific Northwest National Laboratory. The objective of the study is to determine the efficacy of a prototype strobe light system to elicit a negative phototactic response in kokanee and rainbow trout under field conditions. The prototype system consists of six strobe lights affixed to an aluminum frame suspended 15 m vertically underwater from a barge secured in the center of the entrance to the third powerplant forebay. The lights, controlled by a computer, illuminate a region directly upstream of the barge. The 2003 study period extended from June 16 through August 1. Three light treatments were used: all six lights on for 24 hours, all lights off for 24 hours, and three of six lights cycled on and off every hour for 24 hours. These three treatment conditions were assigned randomly

  20. Enhanced antifungal efficacy in experimental invasive pulmonary aspergillosis by combination of AmBisome with Fungizone as assessed by several parameters of antifungal response

    NARCIS (Netherlands)

    M.J. Becker (Martin); S. de Marie (Siem); M.H.A.M. Fens (Marcel); W.C.J. Hop (Wim); H.A. Verbrugh (Henri); I.A.J.M. Bakker-Woudenberg (Irma)

    2002-01-01

    textabstractIn common with a proportion of patients with invasive pulmonary aspergillosis (IPA), the efficacy of AmBisome treatment regimens in our rat model remains suboptimal. To investigate whether this might be the result of initially low antifungal activity of amphotericin B a

  1. Understanding language teacher's culturally responsive teaching self-efficacy and its enhancement through learning study in Chinese reading with young Chinese language learners

    OpenAIRE

    Wong, Wing-yee; 黃詠宜

    2014-01-01

    This dissertation consists of two studies which addressed the issue of teaching young Chinese Language Learners (CLLs) to learn Chinese and their language teacher’s culturally responsive teaching self-efficacy. Young CLLs in Hong Kong mainly came from ethnic minorities of South Asia, the differences between language systems and complicated home languages imposed challenges on their Chinese learning. Frontline Chinese language teachers often encounter difficulties in teaching due to inadequ...

  2. Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice.

    Science.gov (United States)

    van Wamel, Annemieke; Sontum, Per Christian; Healey, Andrew; Kvåle, Svein; Bush, Nigel; Bamber, Jeffrey; de Lange Davies, Catharina

    2016-08-28

    Acoustic cluster therapy (ACT) is a novel approach for ultrasound mediated, targeted drug delivery. In the current study, we have investigated ACT in combination with paclitaxel and Abraxane® for treatment of a subcutaneous human prostate adenocarcinoma (PC3) in mice. In combination with paclitaxel (12mg/kg given i.p.), ACT induced a strong increase in therapeutic efficacy; 120days after study start, 42% of the animals were in stable, complete remission vs. 0% for the paclitaxel only group and the median survival was increased by 86%. In combination with Abraxane® (12mg paclitaxel/kg given i.v.), ACT induced a strong increase in the therapeutic efficacy; 60days after study start 100% of the animals were in stable, remission vs. 0% for the Abraxane® only group, 120days after study start 67% of the animals were in stable, complete remission vs. 0% for the Abraxane® only group. For the ACT+Abraxane group 100% of the animals were alive after 120days vs. 0% for the Abraxane® only group. Proof of concept for Acoustic Cluster Therapy has been demonstrated; ACT markedly increases the therapeutic efficacy of both paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice. PMID:27297780

  3. Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice

    Directory of Open Access Journals (Sweden)

    Melariri P

    2015-02-01

    Full Text Available Paula Melariri,1 Lonji Kalombo,2 Patric Nkuna,2 Admire Dube,2,3 Rose Hayeshi,2 Benhards Ogutu,4,5 Liezl Gibhard,6 Carmen deKock,6 Peter Smith,6 Lubbe Wiesner,6 Hulda Swai2 1Polymers and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Port Elizabeth, South Africa; 2Polymer and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Pretoria, South Africa; 3School of Pharmacy, University of the Western Cape, Bellville, South Africa; 4Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 5Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; 6Division of Pharmacology, University of Cape Town Medical School, Groote Schuur Hospital, Cape Town, South Africa Abstract: Tafenoquine (TQ, a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD-deficient individuals. A microemulsion formulation of TQ (MTQ with sizes <20 nm improved the solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min·µmol/L for reference TQ and MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages of Plasmodium parasites without a corresponding increase in toxicity

  4. Going Below Minimums: The Efficacy of Display Enhanced/Synthetic Vision Fusion for Go-Around Decisions during Non-Normal Operations

    Science.gov (United States)

    Prinzel, Lawrence J., III; Kramer, Lynda J.; Bailey, Randall E.

    2007-01-01

    The use of enhanced vision systems in civil aircraft is projected to increase rapidly as the Federal Aviation Administration recently changed the aircraft operating rules under Part 91, revising the flight visibility requirements for conducting approach and landing operations. Operators conducting straight-in instrument approach procedures may now operate below the published approach minimums when using an approved enhanced flight vision system that shows the required visual references on the pilot's Head-Up Display. An experiment was conducted to evaluate the complementary use of synthetic vision systems and enhanced vision system technologies, focusing on new techniques for integration and/or fusion of synthetic and enhanced vision technologies and crew resource management while operating under these newly adopted rules. Experimental results specific to flight crew response to non-normal events using the fused synthetic/enhanced vision system are presented.

  5. How music training enhances working memory: a cerebrocerebellar blending mechanism that can lead equally to scientific discovery and therapeutic efficacy in neurological disorders

    OpenAIRE

    Vandervert, Larry

    2015-01-01

    Background Following in the vein of studies that concluded that music training resulted in plastic changes in Einstein’s cerebral cortex, controlled research has shown that music training (1) enhances central executive attentional processes in working memory, and (2) has also been shown to be of significant therapeutic value in neurological disorders. Within this framework of music training-induced enhancement of central executive attentional processes, the purpose of this article is to argue...

  6. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance

    DEFF Research Database (Denmark)

    Arciero, Paul J; Edmonds, Rohan; He, Feng;

    2016-01-01

    TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men......Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in...... obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on...

  7. Assessing the efficacy of the healthy eating and lifestyle programme (HELP compared with enhanced standard care of the obese adolescent in the community: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Christie Deborah

    2011-11-01

    Full Text Available Abstract Background The childhood obesity epidemic is one of the foremost UK health priorities. Childhood obesity tracks into adult life and places individuals at considerable risk for diabetes, cardiovascular disease, liver disease and other morbidities. There is widespread need for paediatric lifestyle programmes as change may be easier to accomplish in childhood than later in life. Study Design/Method The study will evaluate the management of adolescent obesity by conducting a Medical Research Council complex intervention phase III efficacy randomised clinical trial of the Healthy Eating Lifestyle Programme within primary care. The study tests a community delivered multi-component intervention designed for adolescents developed from best practice as identified by National Institute for Health and Clinical Excellence. The hospital based pilot reduced body mass index and improved health-related quality of life. Subjects will be individually randomised to receiving either the Healthy Eating Lifestyle Programme (12 fortnightly family sessions or enhanced standard care. Baseline and follow up assessments will be undertaken blind to allocation status. A health economic evaluation is also being conducted. 200 obese young people (13-17 years, body mass index > 98th centile for age and sex will be recruited from primary care within the greater London area. The primary hypothesis is that a motivational and solution-focused family-based weight management programme delivered over 6 months is more efficacious in reducing body mass index in obese adolescents identified in the community than enhanced standard care. The primary outcome will be body mass index at the end of the intervention, adjusted for baseline body mass index, age and sex. The secondary hypothesis is that the Healthy Eating Lifestyle Programme is more efficacious in improving quality of life and psychological function and reducing waist circumference and cardiovascular risk factors in

  8. A ruthenium(ii) based photosensitizer and transferrin complexes enhance photo-physical properties, cell uptake, and photodynamic therapy safety and efficacy.

    Science.gov (United States)

    Kaspler, Pavel; Lazic, Savo; Forward, Sarah; Arenas, Yaxal; Mandel, Arkady; Lilge, Lothar

    2016-04-01

    Metal-based photosensitizers are of interest as their absorption and chemical binding properties can be modified via the use of different ligands. Ru(2+) based photosensitizers are known to be effective photodynamic therapy (PDT) agents against bacteria, whereas use for oncological indications in vivo has not been demonstrated with the same level of evidence. We present data showing that premixing the Ru(2+)-complex TLD1433 with transferrin increases the molar extinction coefficient, including longer activation wavelengths, reduces photobleaching rates, and reduces the toxicity of the complex improving overall PDT efficacy. As the transferrin receptor is upregulated in most malignancies, premixing the Ru(2+) complex with transferrin converts the active pharmaceutical ingredient TLD1433 into a drug of potentially considerable clinical utility. PMID:26947517

  9. A Holy Grail of asthma management: toward understanding how long-acting β2-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids

    Science.gov (United States)

    Giembycz, M A; Kaur, M; Leigh, R; Newton, R

    2007-01-01

    There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS)—i.e. glucocorticoid—and an inhaled long-acting β2-adrenoceptor agonist (LABA) is superior to each component administered as a monotherapy alone in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet 2003, 361: 449–456; N Engl J Med 2007, 356: 775–789) reporting for the ‘TRial of Inhaled STeroids ANd long-acting β2-agonists (TRISTAN)' and ‘TOwards a Revolution in COPD Health (TORCH)' international study groups also demonstrated the superior efficacy of LABA/ICS combination therapies over ICS alone in the clinical management of chronic obstructive pulmonary disease. This finding has been independently confirmed indicating that the therapeutic benefit of LABA/ICS combination therapies is not restricted to asthma and may be extended to other chronic inflammatory diseases of the airways. Despite the unquestionable benefit of LABA/ICS combination therapies, there is a vast gap in our understanding of how these two drugs given together deliver superior clinical efficacy. In this article, we review the history of LABA/ICS combination therapies and critically evaluate how these two classes of drugs might interact at the biochemical level to suppress pro-inflammatory responses. Understanding the molecular basis of this fundamental clinical observation is a Holy Grail of current respiratory diseases research as it could permit the rational exploitation of this effect with the development of new ‘optimized' LABA/ICS combination therapies. PMID:18071293

  10. Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

    NARCIS (Netherlands)

    C. van Bree; A.D. Barten-van Rijbroek; R. Leen; H.M. Rodermond; A.B.P. van Kuilenburg; H.B. Kal

    2009-01-01

    Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether OPEC enhances

  11. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    OpenAIRE

    Ijin Joo; Jung Hoon Kim; Jeong Min Lee; Jin Woo Choi; Joon Koo Han; Byung Ihn Choi

    2014-01-01

    Purpose:

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model.

    Methods:

    This study was appro...

  12. MontanideTM Gel01 ST adjuvant enhances PRRS modified live vaccine efficacy by regulating porcine humoral and cellular immune responses

    Science.gov (United States)

    Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity against PRRSV infection in piglets when used in combination with PRRS modified live vac...

  13. A Pilot Study of the Feasibility and Efficacy of the Strategies to Enhance Positive Parenting (STEPP) Program for Single Mothers of Children with ADHD

    Science.gov (United States)

    Chacko, Anil; Wymbs, Brian T.; Flammer-Rivera, Lizette M.; Pelham, William E.; Walker, Kathryn S.; Arnold, Fran W.; Visweswaraiah, Hema; Swanger-Gagne, Michelle; Girio, Erin L.; Pirvics, Lauma L.; Herbst, Laura

    2008-01-01

    Objective: The Strategies to Enhance Positive Parenting (STEPP) program was developed to address putative factors related to poor engagement in and outcomes following traditional behavioral parent training (BPT) for single mothers of children diagnosed with ADHD. Method: Twelve single mothers of children with ADHD were enrolled in an initial…

  14. Concomitant Administration of Mycobacterium bovis BCG with the Meningococcal C Conjugate Vaccine to Neonatal Mice Enhances Antibody Response and Protective Efficacy

    OpenAIRE

    Brynjolfsson, Siggeir F.; Bjarnarson, Stefania P.; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif

    2011-01-01

    Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM197, in mice primed as neonates, broaden the antibody ...

  15. Redox-Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap-Tops Enhances Efficacy Against Pneumonic Tularemia in Mice.

    Science.gov (United States)

    Lee, Bai-Yu; Li, Zilu; Clemens, Daniel L; Dillon, Barbara Jane; Hwang, Angela A; Zink, Jeffrey I; Horwitz, Marcus A

    2016-07-01

    Effective and rapid treatment of tularemia is needed to reduce morbidity and mortality of this potentially fatal infectious disease. The etiologic agent, Francisella tularensis, is a facultative intracellular bacterial pathogen which infects and multiplies to high numbers in macrophages. Nanotherapeutics are particularly promising for treatment of infectious diseases caused by intracellular pathogens, whose primary host cells are macrophages, because nanoparticles preferentially target and are avidly internalized by macrophages. A mesoporous silica nanoparticle (MSN) has been developed functionalized with disulfide snap-tops that has high drug loading and selectively releases drug intracellularly in response to the redox potential. These nanoparticles, when loaded with Hoechst fluorescent dye, release their cargo exclusively intracellularly and stain the nuclei of macrophages. The MSNs loaded with moxifloxacin kill F. tularensis in macrophages in a dose-dependent fashion. In a mouse model of lethal pneumonic tularemia, MSNs loaded with moxifloxacin prevent weight loss, illness, and death, markedly reduce the burden of F. tularensis in the lung, liver, and spleen, and are significantly more efficacious than an equivalent amount of free drug. An important proof-of-principle for the potential therapeutic use of a novel nanoparticle drug delivery platform for the treatment of infectious diseases is provided. PMID:27246117

  16. Scientific Opinion on the safety and efficacy of Suilectin? (Phaseolus vulgaris lectins as a zootechnical additive for suckling piglets (performance enhancer

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP

    2015-01-01

    Full Text Available The active substance of Suilectin™ is a mixture of five phytohaemagglutinin (PHA isoforms. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP considers that the haemagglutination activity (measured by haemagglutinating units (HAUs does not reflect the biological activity of the additive in a comprehensive way. The additive is intended only for aqueous suspension in water for drinking or in liquid complementary feed for suckling piglets. The FEEDAP Panel concludes that the additive is safe for suckling piglets when used under the proposed conditions of use of 220 HAU/piglet for three days. The Panel also considers that there are no reasons to expect that the dose of 660 HAU/piglet in a single administration would not be safe. The use of Suilectin in accordance with the conditions of use proposed by the applicant is considered to be of no concern for the health of the consumer. Suilectin is not an irritant to skin or eyes and is not a skin sensitiser. However, considering its physical and toxicological properties, there is a potential hazard by inhalation exposure. Considering that PHAs are immunogenic substances, the additive should be considered to be a respiratory sensitiser. The additive is a natural plant substance and its use will not result in a substantial increase in concentration in the environment. Therefore there are no safety concerns for the environment. The FEEDAP Panel cannot conclude on the efficacy of the additive in suckling piglets.

  17. Combination of poly-gamma-glutamate and cyclophosphamide enhanced antitumor efficacy against tumor growth and metastasis in a murine melanoma model.

    Science.gov (United States)

    Kim, Doo-Jin; Kim, Eun-Jin; Lee, Tae-Young; Won, Ji-Na; Sung, Moon-Hee; Poo, Haryoung

    2013-09-28

    Conventional chemotherapeutic regimens often accompany severe side effects and fail to induce complete regression of chemoresistant or relapsing metastatic cancers. The need for establishing more efficacious anticancer strategies led to the development of a combined modality treatment of chemotherapy in conjunction with immunotherapy or radiotherapy. It has been reported that poly-gamma-glutamate (γ-PGA), a natural polymer composed of glutamic acids, increases antitumor activity by activating antigen-presenting cells and natural killer (NK) cells. Here, we investigated the antitumor effect of γ-PGA in combination with cyclophosphamide in a murine melanoma model. Whereas cyclophosphamide alone directly triggered apoptosis of tumor cells in vitro, γ-PGA did not show cytotoxicity in tumor cells. Instead, it activated macrophages, as reflected by the upregulation of surface activation markers and the secretion of proinflammatory factors, such as nitric oxide and tumor necrosis factor α. When the antitumor effects were examined in a mouse model, combined treatment with cyclophosphamide and γ-PGA markedly suppressed tumor growth and metastasis. Notably, γ-PGA treatment dramatically increased the NK cell population in lung tissues, coinciding with decreased metastasis and increased survival. These data collectively suggest that γ-PGA can act as an immunotherapeutic agent that exhibits a synergistic antitumor effect in combination with conventional chemotherapy. PMID:23867701

  18. Enhanced in Vivo Efficacy of a Type I Interferon Superagonist with Extended Plasma Half-life in a Mouse Model of Multiple Sclerosis*

    Science.gov (United States)

    Harari, Daniel; Kuhn, Nadine; Abramovich, Renne; Sasson, Keren; Zozulya, Alla L.; Smith, Paul; Schlapschy, Martin; Aharoni, Rina; Köster, Mario; Eilam, Raya; Skerra, Arne; Schreiber, Gideon

    2014-01-01

    IFNβ is a common therapeutic option to treat multiple sclerosis. It is unique among the family of type I IFNs in that it binds to the interferon receptors with high affinity, conferring exceptional biological properties. We have previously reported the generation of an interferon superagonist (dubbed YNSα8) that is built on the backbone of a low affinity IFNα but modified to exhibit higher receptor affinity than even for IFNβ. Here, YNSα8 was fused with a 600-residue hydrophilic, unstructured N-terminal polypeptide chain comprising proline, alanine, and serine (PAS) to prolong its plasma half-life via “PASylation.” PAS-YNSα8 exhibited a 10-fold increased half-life in both pharmacodynamic and pharmacokinetic assays in a transgenic mouse model harboring the human receptors, notably without any detectable loss in biological potency or bioavailability. This long-lived superagonist conferred significantly improved protection from MOG35–55-induced experimental autoimmune encephalomyelitis compared with IFNβ, despite being injected with a 4-fold less frequency and at an overall 16-fold lower dosage. These data were corroborated by FACS measurements showing a decrease of CD11b+/CD45hi myeloid lineage cells detectable in the CNS, as well as a decrease in IBA+ cells in spinal cord sections determined by immunohistochemistry for PAS-YNSα8-treated animals. Importantly, PAS-YNSα8 did not induce antibodies upon repeated administration, and its biological efficacy remained unchanged after 21 days of treatment. A striking correlation between increased levels of CD274 (PD-L1) transcripts from spleen-derived CD4+ cells and improved clinical response to autoimmune encephalomyelitis was observed, indicating that, at least in this mouse model of multiple sclerosis, CD274 may serve as a biomarker to predict the effectiveness of IFN therapy to treat this complex disease. PMID:25193661

  19. Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I

    Directory of Open Access Journals (Sweden)

    Mian Afsar

    2012-09-01

    Full Text Available Abstract Background Chronic myelogenous leukemia (CML and Philadelphia chromosome-positive (Ph+ acute lymphatic leukemia (Ph + ALL are caused by the t(9;22, which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The constitutively activated BCR/ABL-kinase “escapes” the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. Given the fact that all AKIs fail to inhibit BCR/ABL harboring the ‘gatekeeper’ mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia. Methods The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC from Ph + ALL-patients. Results Here, we show that GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner. Conclusions Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors.

  20. Inhibition of DNA-repair genes Ercc1 and Mgmt enhances temozolomide efficacy in gliomas treatment: a pre-clinical study.

    Science.gov (United States)

    Boccard, Sandra G; Marand, Sandie V; Geraci, Sandra; Pycroft, Laurie; Berger, François R; Pelletier, Laurent A

    2015-10-01

    Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly deleted chromosomal region in oligodendroglioma (1p/19q) highly correlated with patient response to chemotherapy. We measured effects of inhibition of ten DNA-repair genes expression using siRNAs on astrocytoma cell response to cisplatin (CDDP) and TMZ. SiRNAs targeting ercc1, ercc2, mutyh, and pnkp significantly sensitized cells to chemotherapy, increasing cell death by up to 25%. In vivo we observed a decrease of subcutaneous glioma tumor growth after injection of siRNA in conjunction with absorption of TMZ. We demonstrated in this pre-clinical study that targeting of DNA-repair genes such as Ercc1 could be used as an adjuvant chemosensitization treatment, similarly to Mgmt inhibition. PMID:26336131

  1. MUD and Self Efficacy.

    Science.gov (United States)

    Lee, Kwan Min

    2000-01-01

    Proposes a theoretical framework for analyzing the effect of MUD (Multi-User Dungeons) playing on users' self-efficacy by applying Bandura's social learning theory, and introduces three types of self-efficacy: computer self-efficacy; social self-efficacy; and generalized self-efficacy. Considers successful performance, vicarious experience,…

  2. Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay

    2016-03-01

    In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

  3. MicroRNA-1301-Mediated RanGAP1 Downregulation Induces BCR-ABL Nuclear Entrapment to Enhance Imatinib Efficacy in Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Tsung-Yao Lin

    Full Text Available Chronic myeloid leukemia (CML is a myeloproliferative disease. Imatinib (IM, the first line treatment for CML, is excessively expensive and induces various side effects in CML patients. Therefore, it is essential to investigate a new strategy for improving CML therapy. Our immunoblot data revealed that RanGTPase activating protein 1 (RanGAP1 protein levels increased by approximately 30-fold in K562 cells compared with those in normal cells. RanGAP1 is one of the important components of RanGTPase system, which regulates the export of nuclear protein. However, whether RanGAP1 level variation influences BCR-ABL nuclear export is still unknown. In this report, using shRNA to downregulate RanGAP1 expression level augmented K562 cell apoptosis by approximately 40% after treatment with 250 nM IM. Immunofluorescence assay also indicated that three-fold of nuclear BCR-ABL was detected. These data suggest that BCR-ABL nuclear entrapment induced by RanGAP1 downregulation can be used to improve IM efficacy. Moreover, our qRT-PCR data indicated a trend of inverse correlation between the RanGAP1 and microRNA (miR-1301 levels in CML patients. MiR-1301, targeting the RanGAP1 3' untranslated region, decreased by approximately 100-fold in K562 cells compared with that in normal cells. RanGAP1 downregulation by miR-1301 transfection impairs BCR-ABL nuclear export to increase approximately 60% of cell death after treatment of 250 nM IM. This result was almost the same as treatment with 1000 nM IM alone. Furthermore, immunofluorescence assay demonstrated that Tyr-99 of nuclear P73 was phosphorylated accompanied with nuclear entrapment of BCR-ABL after transfection with RanGAP1 shRNA or miR-1301 in IM-treated K562 cells. Altogether, we demonstrated that RanGAP1 downregulation can mediate BCR-ABL nuclear entrapment to activate P73-dependent apoptosis pathway which is a novel strategy for improving current IM treatment for CML.

  4. Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

    Science.gov (United States)

    Aoki, Hajime; Iwao, Yasunori; Mizoguchi, Midori; Noguchi, Shuji; Itai, Shigeru

    2015-05-01

    In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated Helicobacter pylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone. PMID:25703356

  5. Glycyrrhetinic acid-decorated and reduction-sensitive micelles to enhance the bioavailability and anti-hepatocellular carcinoma efficacy of tanshinone IIA.

    Science.gov (United States)

    Chen, Fengqian; Zhang, Jinming; He, Yao; Fang, Xiefan; Wang, Yitao; Chen, Meiwan

    2016-01-01

    It remains a challenge to increase drug tumor-specific accumulation as well as to achieve intracellular-controlled drug release for hepatocellular carcinoma (HCC) chemotherapy. Herein, we developed a dual-functional biodegradable micellar system constituted by glycyrrhetinic acid coupling poly(ethylene glycol)-disulfide linkage-poly(lactic-co-glycolic acid) (GA-PEG-SS-PLGA) to achieve both hepatoma-targeting and redox-responsive intracellular drug release. Tanshinone IIA (TAN IIA), an effective anti-HCC drug, was encapsulated. Notably, it exhibited rapid aggregation and faster drug release in 10 mM dithiothreitol compared with the redox-insensitive control. Furthermore, GA-decorated micelles revealed HCC-specific cellular uptake in human liver cancer HepG2 cells with an energy-dependent manner, in which micropinocytosis and caveolae-mediated endocytosis were demonstrated as the major cellular pathways. The enhanced cytotoxicity and pro-apoptotic effects against HepG2 cells in vitro were observed, mediated by up-regulation of the intracellular ROS level, the increased cell cycle arrest at S phase, enhanced necrocytosis and up-regulation of caspase 3/7, P38 protein expression. In addition, TAN IIA-loaded micelles had a significantly prolonged circulation time, improved bioavailability, and resulted in an increased accumulation of TAN IIA in the liver. With the synergistic effects of HCC-targeting and controlled drug release, TAN IIA-loaded GA-PEG-SS-PLGA micelles significantly inhibited tumor growth and increased survival time in a mouse HCC-xenograft model. Collectively, the GA-PEG-SS-PLGA micelles with HCC-targeting and redox-sensitive characters would provide a novel strategy to deliver TAN IIA effectively for HCC therapy. PMID:26484363

  6. 808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd(3+)-sensitized upconversion emission with enhanced anti-tumor efficacy.

    Science.gov (United States)

    Hou, Zhiyao; Deng, Kerong; Li, Chunxia; Deng, Xiaoran; Lian, Hongzhou; Cheng, Ziyong; Jin, Dayong; Lin, Jun

    2016-09-01

    The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYF4:Yb/Tm@NaYF4:Yb@NaNdF4:Yb@NaYF4 (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiO2, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiO2 shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd(3+)-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual-photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT. PMID:27267626

  7. Amorphous polyphosphate/amorphous calcium carbonate implant material with enhanced bone healing efficacy in a critical-size defect in rats.

    Science.gov (United States)

    Wang, Xiaohong; Ackermann, Maximilian; Wang, Shunfeng; Tolba, Emad; Neufurth, Meik; Feng, Qingling; Schröder, Heinz C; Müller, Werner E G

    2016-01-01

    In this study the effect of amorphous calcium carbonate (ACC) microparticles and amorphous calcium polyphosphate (polyP) microparticles (termed aCa-polyP-MP) on bone mineral forming cells/tissue was investigated in vitro and in vivo. The ACC particles (termed ACC-P10-MP) were prepared in the presence of Na-polyP. Only the combinations of polyP and ACC microparticles enhanced the proliferation rate of human mesenchymal stem cells (MSCs). Gene expression studies revealed that ACC causes an upregulation of the expression of the cell membrane-associated carbonic anhydrase IX (CA IX; formation of ACC), while the transcript level of the alkaline phosphatase (ALP; liberation of orthophosphate from polyP) changes only relatively little. In contrast, aCa-polyP-MP primarily induces ALP expression. If both components are applied together a strong stimulation of expression of both marker genes is observed. In order to investigate whether ACC also enhances bone regeneration induced by polyP in vivo, the particles were encapsulated into PLGA (poly(d,l-lactide-co-glycolide)) microspheres (diameter ~800 μm) and implanted into rat critical-size calvarial defects. The studies revealed that animals that received aCa-polyP-MP microspheres showed an increased rate of regeneration compared to β-tri-calcium phosphate (β-TCP) controls. This effect is even accelerated if microspheres with both aCa-polyP-MP and ACC-P10-MP (1 : 1 weight ratio) are applied, resulting in an almost complete restoration of the defect area after 12 weeks. qRT-PCR analyses of tissue sections through the regeneration zone with microspheres containing both aCa-polyP-MP and ACC-P10-MP revealed a significantly higher upregulation of expression of the marker genes compared to each of the components alone. The Young's moduli for microspheres containing aCa-polyP-MP (1.74 MPa) and aCa-polyP-MP/ACC-P10-MP (2.38 MPa) were markedly higher compared to β-TCP-controls (0.63 mPa). Our results show that the combined

  8. Principals' transformational leadership and teachers' collective efficacy.

    Science.gov (United States)

    Dussault, Marc; Payette, Daniel; Leroux, Mathieu

    2008-04-01

    The study was designed to test the relationship of principals' transformational, transactional, and laissez-faire leadership with teachers' collective efficacy. Bandura's theory of efficacy applied to the group and Bass's transformational leadership theory were used as the theoretical framework. Participants included 487 French Canadian teachers from 40 public high schools. As expected, there were positive and significant correlations between principals' transformational and transactional leadership and teachers' collective efficacy. Also, there was a negative and significant correlation between laissez-faire leadership and teachers' collective efficacy. Moreover, regression analysis showed transformational leadership significantly enhanced the predictive capabilities of transactional leadership on teachers' collective efficacy. These results confirm the importance of leadership to predict collective efficacy and, by doing so, strengthen Bass's theory of leadership. PMID:18567210

  9. Co-expression of the C-terminal domain of Yersinia enterocolitica invasin enhances the efficacy of classical swine-fever-vectored vaccine based on human adenovirus

    Indian Academy of Sciences (India)

    Helin Li; Pengbo Ning; Zhi Lin; Wulong Liang; Kai Kang; Lei He; Yanming Zhang

    2015-03-01

    The use of adenovirus vector-based vaccines is a promising approach for generating antigen-specific immune responses. Improving vaccine potency is necessary in other approaches to address their inadequate protection for the majority of infectious diseases. This study is the first to reconstruct a recombinant replication-defective human adenovirus co-expressing E2 and invasin C-terminal (InvC) glycoproteins (rAd-E2-InvC). rAd-E2-InvC with 2×106 TCID50 was intramuscularly administered two times to CSFV-free pigs at 14 day intervals. No adverse clinical reactions were observed in any of the pigs after the vaccination. The CSFV E2-specific antibody titer was significantly higher in the rAd-E2-InvC group than that in the rAdV-E2 group as measured by NPLA and blocking ELISA. Pigs immunized with rAd-E2-InvC were completely protected against lethal challenge. Neither CSFV RNA nor pathological changes were detected in the tissues after CSFV challenge. These results demonstrate that rAd-E2-InvC could be an alternative to the existing CSF vaccine. Moreover, InvC that acts as an adjuvant could enhance the immunogenicity of rAdV-E2 and induce high CSFV E2-specific antibody titer and protection level.

  10. Diagnostic Efficacy of All Series of Dynamic Contrast Enhanced Breast MR Images Using Gradient Vector Flow (GVF Segmentation and Novel Border Feature Extraction for Differentiation Between Malignant

    Directory of Open Access Journals (Sweden)

    L. Bahreini

    2010-12-01

    Full Text Available Background/Objective: To discriminate between malignant and benign breast lesions;"nconventionally, the first series of Breast Subtraction Dynamic Contrast-Enhanced Magnetic"nResonance Imaging (BS DCE-MRI images are used for quantitative analysis. In this study, we"ninvestigated whether using all series of these images could provide us with more diagnostic"ninformation."nPatients and Methods: This study included 60 histopathologically proven lesions. The steps of"nthis study were as follows: selecting the regions of interest (ROI, segmentation using Gradient"nVector Flow (GVF snake for the first time, defining new feature sets, using artificial neural network"n(ANN for optimal feature set selection, evaluation using receiver operating characteristic (ROC"nanalysis."nResults: The results showed GVF snake method correctly segmented 95.3% of breast lesion"nborders at the overlap threshold of 0.4. The first classifier which used the optimal feature set"nextracted only from the first series of BS DCE-MRI images achieved an area under the curve"n(AUC of 0.82, specificity of 60% at sensitivity of 81%. The second classifier which used the same"noptimal feature set but was extracted from all five series of these images achieved an AUC of"n0.90, specificity of 79% at sensitivity of 81%."nConclusion: The result of GVF snake segmentation showed that it could make an accurate"nsegmentation in the borders of breast lesions. According to this study, using all five series of BS"nDCE-MRI images could provide us with more diagnostic information about the breast lesion and"ncould improve the performance of breast lesion classifiers in comparison with using the first"nseries alone.

  11. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine

    Directory of Open Access Journals (Sweden)

    Warhurst David C

    2003-09-01

    Full Text Available Abstract Background Chloroquine accumulates in the acidic digestive vacuole of the intraerythrocytic malaria parasite, and prevents the detoxication of haematin released during haemoglobin digestion. Changes in protein PfCRT in the digestive vacuole membrane of growing intra-erythrocytic stages of Plasmodium falciparum are crucial for resistance. Expressed in yeast, PfCRT resembles an anion channel. Depressed anion channel function could increase intralysosomal pH to reduce entry of basic drug, or enhanced function could reduce drug interaction with target haematin. The most important resistance-associated change is from positively-charged lysine-76 to neutral threonine which could facilitate drug efflux through a putative channel. It has been proposed that the resistance-reversing effect of verapamil is due to hydrophobic binding to the mutated PfCRT protein, and replacement of the lost positive charge, which repels the access of 4-aminoquinoline cations, thus partially restoring sensitivity. Desethylamodiaquine, the active metabolite of amodiaquine, which has significant activity in chloroquine-resistance, may also act similarly on its own. Methods Changes in physicochemical parameters in different CQ-resistant PfCRT sequences are analysed, and correlations with drug activity on lines transfected with different alleles of the pfcrt gene are examined. Results and conclusions The results support the idea that PfCRT is a channel which, in resistant parasites, can allow efflux of chloroquine from the digestive vacuole. Activity of the chloroquine/verapamil combination and of desethylamodiaquine both correlate with the mean hydrophobicity of PfCRT residues 72-76. This may partly explain clinical-resistance to amodiaquine found in the first chloroquine-resistant malaria cases from South America and enables tentative prediction of amodiaquine's clinical activity against novel haplotypes of PfCRT.

  12. Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

    Science.gov (United States)

    Yang, Xiaoliang; Saito, Ryuta; Nakamura, Taigen; Zhang, Rong; Sonoda, Yukihiko; Kumabe, Toshihiro; Forsayeth, John; Bankiewicz, Krystof; Tominaga, Teiji

    2016-03-01

    In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells. PMID:24865286

  13. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-03-15

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

  14. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    International Nuclear Information System (INIS)

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

  15. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs

    Science.gov (United States)

    Hiremath, Jagadish; Kang, Kyung-il; Xia, Ming; Elaish, Mohamed; Binjawadagi, Basavaraj; Ouyang, Kang; Dhakal, Santosh; Arcos, Jesus; Torrelles, Jordi B.; Jiang, X.; Lee, Chang Won; Renukaradhya, Gourapura J.

    2016-01-01

    Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs. PMID:27093541

  16. Local radiative treatment of hepatocellular cancer with phosphorus-32 glassmicrospheres to enhance the efficacy of hepatic artery chemoembolism andpossibly related with MDR expressed P-glycoprotein

    Institute of Scientific and Technical Information of China (English)

    Zao Jiang; Lu Liu; Wen Fang; Wei Zhang Shou; Dong Sheng Zhang; Mei Mei Dai

    2000-01-01

    .05, Chi-squaur test). The median survival period ofthe patients were 532 and 564 d in group Ⅰ and Ⅱ respectivcey (Kaplan-Meire method).CONCLUSION The enhanced effectiveness of the local treatment of 32 P-GMS conjugated withchemotherapeutics may be related to the local action on the MDR expressed p-glycoprotein.

  17. Chief Joseph Kokanee Enhancement Project; Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at Grand Coulee Dam Third Powerplant Forebay, 2005-2006 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, M.; Johnson, Robert; McKinstry, C. [Pacific Northwest National Laboratory

    2006-03-01

    The construction of Grand Coulee and Chief Joseph dams on the Columbia River resulted in the complete extirpation of the anadromous fishery upstream of these structures. Today, this area is totally dependent upon resident fish resources to support local fisheries. The resident fishing is enhanced by an extensive stocking program for target species in the existing fishery, including kokanee (Oncorhynchus nerka kennerlyi) and rainbow trout (O. mykiss). The kokanee fishery in Lake Roosevelt has not been meeting the return goals set by fisheries managers despite the stocking program. Investigations of physical and biological factors that could affect the kokanee population found predation and entrainment had a significant impact on the fish population. In 1999 and 2000, walleye (Sander vitreum) consumed between 15% and 9%, respectively, of the hatchery kokanee within 41 days of their release, while results from a study in the late 1990s estimated that entrainment at Grand Coulee Dam could account for up to 30% of the total mortality of the stocked fish. To address the entrainment loss, the Bonneville Power Administration commissioned a study to determine if fish would avoid areas illuminated by strobe lights in the forebay of the third powerplant. This work was conducted by Pacific Northwest National Laboratory (PNNL) in conjunction with the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes). From 2002 through 2004, six strobe lights were suspended in the center of the opening to the third powerplant forebay during summer months. Results from those studies indicated that fish appeared to be attracted to the illuminated area but only at night and when flow conditions within the third powerplant forebay were minimal. However, small but consistent results from these studies indicated that under high flow conditions, fish might be avoiding the lights. The 2005 study was designed to examine whether, under high flow conditions near the penstock

  18. Enhanced Th1-biased immune efficacy of porcine circovirus type 2 Cap-protein-based subunit vaccine when coadministered with recombinant porcine IL-2 or GM-CSF in mice.

    Science.gov (United States)

    Wang, Yiping; Lu, Yuehua; Liu, Dan; Wei, Yanwu; Guo, Longjun; Wu, Hongli; Huang, Liping; Liu, Jianbo; Liu, Changming

    2015-02-01

    Porcine circovirus type 2 (PCV2) capsid (Cap) protein is the primary protective antigen responsible for inducing PCV2-specific protective immunity, so it is a desirable target for the development of recombinant subunit vaccines to prevent PCV2-associated diseases. Interleukin 2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF), used as immune adjuvants, have been shown to enhance the immunogenicity of certain antigens or vaccines in various experimental models. In this study, five different subunit vaccines (the PCV2-Cap, Cap-PoIL-2, PCV2-Cap + PoIL-2, Cap-PoGM-CSF, and PCV2-Cap + PoGM-CSF vaccines) were prepared based on baculovirus-expressed recombinant proteins. The immunogenicity of these vaccines was evaluated to identify the immunoenhancement by PoIL-2 and PoGM-CSF of the Cap-protein-based PCV2 subunit vaccine in mice. The PCV2-Cap + PoIL-2, Cap-PoGM-CSF, PCV2-Cap + PoGM-CSF, and PCV2-Cap vaccines induced significantly higher levels of PCV2-specific antibodies than the Cap-PoIL-2 vaccine, whereas there was no apparent difference between these four vaccines. Our results indicate that neither PoIL-2 nor PoGM-CSF had effect on the enhancement of the humoral immunity induced by the PCV2-Cap vaccine. Furthermore, the PCV2-Cap + PoIL-2, Cap-PoGM-CSF, and PCV2-Cap + PoGM-CSF vaccines elicited stronger lymphocyte proliferative responses and greater IL-2 and interferon gamma (IFN-γ) secretion. This suggests that PoIL-2 and PoGM-CSF substantially augmented the Th1-biased immune response to the PCV2-Cap vaccine. Following challenge, the viral loads in the lungs of the PCV2-Cap + PoIL-2-, Cap-PoGM-CSF-, and PCV2-Cap + PoGM-CSF-treated groups were dramatically lower than those in the Cap-PoIL-2- and PCV2-Cap-treated groups, indicating that the three vaccines induced stronger protective effects against challenge. These findings show that PoIL-2 and PoGM-CSF essentially enhanced the Th1-biased protective efficacy of the

  19. Knockdown of delta-5-desaturase promotes the anti-cancer activity of dihomo-γ-linolenic acid and enhances the efficacy of chemotherapy in colon cancer cells expressing COX-2.

    Science.gov (United States)

    Xu, Yi; Yang, Xiaoyu; Zhao, Pinjing; Yang, Zhongyu; Yan, Changhui; Guo, Bin; Qian, Steven Y

    2016-07-01

    Cyclooxygenase (COX), commonly overexpressed in cancer cells, is a major lipid peroxidizing enzyme that metabolizes polyunsaturated fatty acids (ω-3s and ω-6s). The COX-catalyzed free radical peroxidation of arachidonic acid (ω-6) can produce deleterious metabolites (e.g. 2-series prostaglandins) that are implicated in cancer development. Thus, COX inhibition has been intensively investigated as a complementary therapeutic strategy for cancer. However, our previous study has demonstrated that a free radical-derived byproduct (8-hydroxyoctanoic acid) formed from COX-catalyzed peroxidation of dihomo-γ-linolenic acid (DGLA, the precursor of arachidonic acid) can inhibit colon cancer cell growth. We thus hypothesize that the commonly overexpressed COX in cancer (~90% of colon cancer patients) can be taken advantage to suppress cell growth by knocking down delta-5-desaturase (D5D, a key enzyme that converts DGLA to arachidonic acid). In addition, D5D knockdown along with DGLA supplement may enhance the efficacy of chemotherapeutic drugs. After knocking down D5D in HCA-7 colony 29 cells and HT-29 cells (human colon cancer cell lines with high and low COX levels, respectively), the antitumor activity of DGLA was significantly enhanced along with the formation of a threshold range (~0.5-1.0μM) of 8-hydroxyoctanoic acid. In contrast, DGLA treatment did not inhibit cell growth when D5D was not knocked down and only limited amount of 8-hydroxyoctanoic acid was formed. D5D knockdown along with DGLA treatment also enhanced the cytotoxicities of various chemotherapeutic drugs, including 5-fluorouracil, regorafenib, and irinotecan, potentially through the activation of pro-apoptotic proteins, e.g. p53 and caspase 9. For the first time, we have demonstrated that the overexpressed COX in cancer cells can be utilized in suppressing cancer cell growth. This finding may provide a new option besides COX inhibition to optimize cancer therapy. The outcome of this translational

  20. Enhancement of insecticide efficacy by adipokinetic hormones

    Czech Academy of Sciences Publication Activity Database

    Kodrík, Dalibor; Plavšin, Ivana; Velki, Mirna; Stašková, Tereza

    New York: NovaScience Publishers,Inc, 2015 - (Montgomery, J.), s. 77-91 ISBN 978-1-63483-475-9 R&D Projects: GA ČR GA14-07172S Institutional support: RVO:60077344 Keywords : adipokinetic hormones Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection

  1. Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy

    Science.gov (United States)

    Deng, Xiaoran; Chen, Yinyin; Cheng, Ziyong; Deng, Kerong; Ma, Ping'an; Hou, Zhiyao; Liu, Bei; Huang, Shanshan; Jin, Dayong; Lin, Jun

    2016-03-01

    Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of ``killing three birds with one stone'', that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of ``gate molecules'' for controlled drug release by 650 nm laser radiation

  2. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    Science.gov (United States)

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  3. INTERACTIVE EFFECTS OF TEAM COHESION ON PERCEIVED EFFICACY IN SEMI-PROFESSIONAL SPORT

    Directory of Open Access Journals (Sweden)

    Francisco Miguel Leo Marcos

    2010-06-01

    Full Text Available The present study examined the relationships among cohesion, self-efficacy, coaches' perceptions of their players' efficacy at the individual level and athletes' perceptions of their teammates' efficacy. Participants (n = 76 recruited from four semi- professional soccer and basketball teams completed cohesiveness and efficacy questionnaires who. Data were analyzed through a correlational methodology. Results indicated significant correlations between self-efficacy and task cohesion and social cohesion. Regression analysis results suggest task cohesion positively related to coaches and teammate´s perception of efficacy. These results have implications for practitioners in terms of the importance of team building to enhance team cohesion and feelings of efficacy

  4. Efficacy of bilateral pallidotomy.

    Science.gov (United States)

    Kim, R; Alterman, R; Kelly, P J; Fazzini, E; Eidelberg, D; Beric, A; Sterio, D

    1997-03-15

    Unilateral pallidotomy is a safe and effective treatment for medically refractory bradykinetic Parkinson's disease, especially in those patients with levodopa-induced dyskinesia and severe on-off fluctuations. The efficacy of bilateral pallidotomy is less certain. The authors completed 11 of 12 attempted bilateral pallidotomies among 150 patients undergoing pallidotomy at New York University. In all but one patient, the pallidotomies were separated by at least 9 months. Patients were selected for bilateral pallidotomy if they exhibited bilateral rigidity, bradykinesia, or levodopa-induced dyskinesia prior to treatment or if they exhibited disease progression contralateral to their previously treated side. The Unified Parkinson's Disease Rating Scale (UPDRS) and timed upper-extremity tasks of the Core Assessment Protocol for Intracerebral Transplantation (CAPIT) were administered to all 12 patients in the "off" state (12 hours without receiving medications) preoperatively and again at 6 and 12 months after each procedure. The median UPDRS and contralateral CAPIT scores improved 60% following the initial procedure (p = 0.008, Wilcoxon rank sums test). The second pallidotomy generated only an additional 10% improvement in the UPDRS and CAPIT scores ipsilateral to the original procedure (p = 0.05). Worsened speech was observed in two cases. In the 12th case, total speech arrest was noted during test stimulation. Speech returned within minutes after stimulation was halted. Lesioning was not performed. These results indicate that bilateral pallidotomy has a narrow therapeutic window. Motor improvement ipsilateral to the first lesion leaves little room for further improvement from the second lesion and the risk of speech deficit is greatly enhanced. Chronic pallidal stimulation contralateral to a previously successful pallidotomy may prove to be a safer alternative for the subset of patients who require bilateral procedures. PMID:15096015

  5. Effects of Enhanced Self-efficacy Interventions on Self-management for Middle-aged Hypertensive Patients%增强自我效能干预对中年高血压患者自我管理能力的效果评价

    Institute of Scientific and Technical Information of China (English)

    李艳红; 张振香; 李平; 张秋实; 林蓓蕾; 郑蔚; 李俊玲; 陈颖; 徐燕茹

    2013-01-01

    Objective To explore the effects of enhanced self - efficacy intervention on self - management for middle- aged patients with hypertension. Methods A total of 200 middle - aged hypertensive patients were randomly divided into control group ( n = 100 ) and intervention group ( n = 100 ). Conventional intervention was taken in control group and enhanced self- efficacy intervention was applied in intervention group. The self - efficacy intervention included group classes, providing health education manual, peer education, family participation. Before and after 12 months intervention, the scores of self- management, self - efficacy and blood pressure were measured. Results There were no significant differences in the baseline measures between two groups. Significant differences were found at 12 months after intervention between groups in scores of self -efficacy control ( 43. 89 ±7. 66 ) vs. intervention ( 49. 96 ± 5. 31 ) and self - management control ( 47. 37 ± 8. 49 ) vs. intervention ( 56. 72 ±7. 37 ). Other significant differences were systolic blood pressure control ( 138. 21 ± 15. 68 ) vs. intervention ( 130. 03 ± 14. 63 ) mm Hg and diastolic blood pressure control ( 84. 43 ±7. 38 ) mm Hg vs. intervention ( 79. 24 ±7. 89 ) mm Hg. The rate of blood pressure control was 66. 3% , 78.4% (P=0. 06). Conclusion Self - efficacy enhancing interventions have positive effects on self - management and blood pressure control for middle - aged hypertensive patients.%目的 探讨增强自我效能干预对中年高血压患者自我管理能力的影响.方法 将200例经住院治疗、出院后符合纳入标准的中年高血压患者按随机数字表法分为对照组和干预组,各100例,对照组给予常规出院指导和随访,干预组采取增强自我效能干预,包括小组授课、发放健康教育手册、同伴教育、家属参与等干预形式.分别在干预前及干预12个月末评价自我效能、自我管理

  6. Effects of Self-Regulated Vocabulary Learning Process on Self-Efficacy

    Science.gov (United States)

    Mizumoto, Atsushi

    2013-01-01

    Researchers, especially in the field of educational psychology, have argued that self-efficacy plays an important role in self-regulated learning. As such, teaching of self-regulated learning often focuses on enhancing self-efficacy. However, few studies have examined how the process of self-regulated learning might lead to the enhancement of…

  7. Efficacy of climate forcings

    Science.gov (United States)

    Hansen, J.; Sato, M.; Ruedy, R.; Nazarenko, L.; Lacis, A.; Schmidt, G. A.; Russell, G.; Aleinov, I.; Bauer, M.; Bauer, S.; Bell, N.; Cairns, B.; Canuto, V.; Chandler, M.; Cheng, Y.; Del Genio, A.; Faluvegi, G.; Fleming, E.; Friend, A.; Hall, T.; Jackman, C.; Kelley, M.; Kiang, N.; Koch, D.; Lean, J.; Lerner, J.; Lo, K.; Menon, S.; Miller, R.; Minnis, P.; Novakov, T.; Oinas, V.; Perlwitz, Ja.; Perlwitz, Ju.; Rind, D.; Romanou, A.; Shindell, D.; Stone, P.; Sun, S.; Tausnev, N.; Thresher, D.; Wielicki, B.; Wong, T.; Yao, M.; Zhang, S.

    2005-09-01

    We use a global climate model to compare the effectiveness of many climate forcing agents for producing climate change. We find a substantial range in the "efficacy" of different forcings, where the efficacy is the global temperature response per unit forcing relative to the response to CO2 forcing. Anthropogenic CH4 has efficacy ˜110%, which increases to ˜145% when its indirect effects on stratospheric H2O and tropospheric O3 are included, yielding an effective climate forcing of ˜0.8 W/m2 for the period 1750-2000 and making CH4 the largest anthropogenic climate forcing other than CO2. Black carbon (BC) aerosols from biomass burning have a calculated efficacy ˜58%, while fossil fuel BC has an efficacy ˜78%. Accounting for forcing efficacies and for indirect effects via snow albedo and cloud changes, we find that fossil fuel soot, defined as BC + OC (organic carbon), has a net positive forcing while biomass burning BC + OC has a negative forcing. We show that replacement of the traditional instantaneous and adjusted forcings, Fi and Fa, with an easily computed alternative, Fs, yields a better predictor of climate change, i.e., its efficacies are closer to unity. Fs is inferred from flux and temperature changes in a fixed-ocean model run. There is remarkable congruence in the spatial distribution of climate change, normalized to the same forcing Fs, for most climate forcing agents, suggesting that the global forcing has more relevance to regional climate change than may have been anticipated. Increasing greenhouse gases intensify the Hadley circulation in our model, increasing rainfall in the Intertropical Convergence Zone (ITCZ), Eastern United States, and East Asia, while intensifying dry conditions in the subtropics including the Southwest United States, the Mediterranean region, the Middle East, and an expanding Sahel. These features survive in model simulations that use all estimated forcings for the period 1880-2000. Responses to localized forcings, such

  8. Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection.

    Science.gov (United States)

    Chitradevi, Sekar Tamil Selvi; Kaur, Gurpreet; Uppalapati, Sivaramakrishna; Yadav, Anandprakash; Singh, Dependrapratap; Bansal, Anju

    2015-11-01

    Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants. PMID:25640657

  9. Enhanced protective efficacy against Mycobacterium tuberculosis afforded by BCG prime-DNA boost regimen in an early challenge mouse model is associated with increased splenic interleukin-2-producing CD4 T-cell frequency post-vaccination.

    Science.gov (United States)

    Kang, Han; Yuan, Qin; Ma, Hui; Hu, Zhi-Dong; Han, De-Ping; Wu, Kang; Lowrie, Douglas B; Fan, Xiao-Yong

    2014-12-01

    The development of improved vaccines and vaccination strategies against Mycobacterium tuberculosis has been hindered by a limited understanding of the immune correlates of anti-tuberculosis protective immunity. Simple measurement of interferon-γ frequency or production per se does not provide adequate prediction of immune protection. In this study, we examined the relationship between T-cell immune responses and protective efficacy conferred by the heterologous vaccination strategy, bacillus Calmette-Guérin (BCG) prime-Ag85A DNA boost (B/D), in an early challenge mouse model of pulmonary tuberculosis. The results demonstrated that mice vaccinated with the B/D regimen had a significantly reduced bacillary load compared with BCG-vaccinated mice, and the reduction in colony-forming units was associated with decreased pathology and lower levels of inflammatory cytokines in the infected lungs. Further analysis of immunogenicity showed that the superior protection afforded by the B/D regimen was associated with significantly increased frequency of splenic interleukin-2 (IL-2) -producing CD4 T cells and increased IL-2 production when measured as integrated mean fluorescence intensity post-vaccination as well. These data suggest that measurement of elevated frequency of IL-2-producing CD4 T cells or IL-2 production in the spleens of vaccinated mice can predict vaccine efficacy, at least in the B/D strategy, and add to the accumulating body of evidence suggesting that BCG prime-boost strategies may be a useful approach to the control of M. tuberculosis infection. PMID:24965530

  10. Impact of Transformational Leadership on Follower’s Self-efficacy

    OpenAIRE

    Jyoti Aggarwal; Krishnan, Venkat R.

    2013-01-01

    Enhancing the belief in the abilities of employees to perform a particular task is the critical role played by a transformational leader subject to impression management strategies used by the employees. The purpose of this article is to report a study on how self-efficacy of the subordinates is enhanced by their use of impression management strategies on supervisors and the impact of transformational leadership in enhancing subordinate’s self-efficacy. Data were collected from 112 responde...

  11. 增强自我效能干预对癫痫患者自尊、总体幸福感及应对方式的影响%The effect of enhancing self-efficacy intervention on self-esteem, overall well-being and coping Styles of patients With epilepsy

    Institute of Scientific and Technical Information of China (English)

    刘桂苓; 楚平华

    2010-01-01

    Objective To explore the effect of enhancing self-efficacy intervention on self-esteem, overall well-being and coping styles of patients with epilepsy. Methods A total of 112 patients with epilepsy were randomly divided into the study group and control group, the control group was given the general health education, and the study groups was given the enhancing self-efficacy intervention, including incentives, social suppor, behavioral approach. Use of The self-esteem scale (SES) and the feelings of inadequacy scale (F1S) , the overall well-being scale (GWB) , and coping style questionnaires was used to evaluate the therapeutic effect before and after training in patients with self-control and two sets of cross-referencing, when the patient was discharged a year impact Results After intervention the SES, FIS, and GWB scores of study group were significantly higher than those of control group , and the immature coping styles scores of study group (self-blame, fantasy, retreat) were significantly lower than those of the control group (P < 0. 01) . Conclusions To enhance self-efficacy intervention, eliminate low self-esteem, enhance their self-confidence and self-esteem and cope with a positive approach to solve the problem can significantly improve the overall well-being in patients with epilepsy.%目的 探讨增强自我效能干预对癫痫患者自尊、总体幸福感及应对方式的影响.方法 将112例癫痫患者随机均分为研究组和对照组,对照组实施一般健康教育,研究组进行增强自我效能干预,内容包括:激励、社会支持、行为方法.学习采用集体授课和个别教育相结合的形式.采用自尊量表(SES)和缺陷感量表(FIS)、总体幸福感量表(GWB)及应付方式问卷对患者进行训练前后自身对照和两组相互对照,在患者出院1年时进行效果评价.结果 研究组经干预治疗后SES、FIS及GWB评分均明显高于对照组,不成熟的应付方式(自责、幻想、

  12. Depression and AIDS Preventive Self-efficacy Among Taiwanese Adolescents.

    Science.gov (United States)

    Lee, Yi-Hui; Salman, Ali

    2016-02-01

    Effectively reducing adolescents' risky sexual behaviors has been an urgent need since the HIV/AIDS infections among young people has been acknowledged as a priority. Self-efficacy has been considered playing an essential role in behavioral changes, and depressed individuals may demonstrate lower self-efficacy. The purpose of this cross-sectional study was to gain insights into self-reported depression among 16-18 years-old Taiwanese adolescents as well as to explore psychosocial predictors of AIDS preventive self-efficacy. A convenience sample of 734 adolescents from southern Taiwan was recruited, and several reliable and valid questionnaires were used to collect data. Descriptive statistics, odds ratio, independent t-test, and hierarchical multiple regression analyses were utilized to analyze data. Results showed that the differences in self-reported depression and in the AIDS preventive self-efficacy varied by gender, substance use, and having sexual experience. Furthermore, depression was a significant predictor of AIDS preventive self-efficacy while controlling the covariates. This study suggests that gender and mental health status such as depression may play significant roles in AIDS preventive self-efficacy. Nurses and health care providers should take the influence of mental health into consideration when designing AIDS preventive interventions for male and female Taiwanese adolescents. The provided information may also enhance psychiatric nurses' capability to provide care and to enhance the prevention of HIV infection for adolescents. PMID:26804507

  13. Exogenous Restoration of TUSC2 Expression Induces Responsiveness to Erlotinib in Wildtype Epidermal Growth Factor Receptor (EGFR Lung Cancer Cells through Context Specific Pathways Resulting in Enhanced Therapeutic Efficacy.

    Directory of Open Access Journals (Sweden)

    Bingbing Dai

    Full Text Available Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC cell lines resistant to the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression. TUSC2-erlotinib cooperativity in vitro could be reproduced in vivo in subcutaneous tumor growth and lung metastasis formation lung cancer xenograft mouse models. Combination treatment with intravenous TUSC2 nanovesicles and erlotinib synergistically inhibited tumor growth and metastasis, and increased apoptotic activity. High-throughput qRT-PCR array analysis enabling multi-parallel expression profile analysis of eighty six receptor and non-receptor tyrosine kinase genes revealed a significant decrease of FGFR2 expression level, suggesting a potential role of FGFR2 in TUSC2-enhanced sensitivity to erlotinib. Western blots showed inhibition of FGFR2 by TUSC2 transient transfection, and marked increase of PARP, an apoptotic marker, cleavage level after TUSC2-erlotinb combined treatment. Suppression of FGFR2 by AZD4547 or gene knockdown enhanced sensitivity to erlotinib in some but not all tested cell lines. TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. These results suggest that TUSC2 restoration in wild type EGFR NSCLC may overcome erlotinib resistance, and identify FGFR2 and mTOR as critical regulators of this activity in varying cellular contexts. The therapeutic activity of TUSC2 could extend the use of erlotinib to lung cancer patients with wildtype EGFR.

  14. 增强自我效能联合抚触护理对妊娠高血压产妇心理应激反应及妊娠结局影响%Enhance self-efficacy joint touch care of gestational hypertension maternal psychological stress reaction and pregnancyoutcome

    Institute of Scientific and Technical Information of China (English)

    陶兰; 吴春燕; 顾珺; 蒋兰芳

    2015-01-01

    目的 探讨增强自我效能联合抚触护理对妊娠高血压产妇心理应激反应及妊娠结局影响.方法 将收治的124例妊娠高血压产妇随机分为两组各62例,对照组给予围产期间给予常规性护理,观察组应用增强自我效能联合抚触护理,对比分析两组产妇心理应激反应、产程的差异.结果 观察组干预后收缩压、舒张压、心率水平显著低于对照组(P<0.05).观察组干预后汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评分显著低于对照组(P<0.05).观察组剖宫产率、产妇产后出血率、新生儿窒息率低于对照组(P<0.05).结论 增强自我效能联合抚触护理能有效减轻妊娠高血压产妇分娩前心理应激反应及负性情绪,减少母婴不良妊娠结局发生率.%Objective To study the enhancing self-efficacy joint touch care of gestational hypertension maternal psychological stress reaction,effect on pregnancy outcome.Methods 124 cases of pregnancy-induced hypertension maternal were randomly divided into two group (n =62),the control group given during among given routine nursing care,observation group application of combined touch nursing enhance self-efficacy,compared two groups of maternal psychological stress reaction and labor.Results Observation group after the intervention systolic pressure,diastolic blood pressure and heart rate was significantly lower than control group (P< 0.05).Observation group after the intervention HAMA and HAMD score was significantly lower than control group (P< 0.05).Observation group cesarean section rate,rate of maternal postpartum hemorrhage,neonatal asphyxia rate was lower than the control group (P< 0.05).Conclusion Enhancing self-efficacy joint touch nursing can effectively reduce pregnancy-induced hypertension maternal psychological stress and negative emotions before delivery,reduce the incidence of maternal and infant adverse pregnancy outcomes,improve family satisfaction.

  15. Pre-irradiation with low-dose 12C6+ beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    Science.gov (United States)

    Liu, Bing; Zhang, Hong; Li, Wenjian; Li, Qiang; Zhou, Guangming; Xie, Yi; Hao, Jifang; Min, Fengling; Zhou, Qingming; Duan, Xin

    2007-04-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30% 60%, 20% 130% and 30% 70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  16. Pre-irradiation with low-dose 12C6+beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were signifi-cantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30%-60%, 20%-130% and 30%-70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

  17. 超声血管增强技术在布-加综合征支架置入术后疗效评估中的应用%Application of vascular enhancement technology in the evaluation of therapeutic efficacy of stenting for Budd-Chiari syndrome

    Institute of Scientific and Technical Information of China (English)

    王荣; 王兴田; 亓培君; 祖茂衡

    2013-01-01

    目的 探讨超声血管增强技术(VET)在布-加综合征(BCS)支架置入术后疗效评估中的应用价值.方法 对39例BCS置入支架患者共41个支架进行二维超声、彩色多普勒及VET检查,存储支架及所在血管的静态及动态图像,比较血管内支架的二维与VET图像质量.对超声检查发现的支架狭窄的患者行数字减影血管造影(DSA)检查,测量支架内血栓范围,并与VET检查结果进行比较.结果 VET技术显示血管内支架图像质量评分高于二维超声,二者比较差异有统计学意义.VET显示的支架内血栓范围与DSA结果相近.结论 VET可改善血管内支架的清晰度,与彩色多普勒相结合,提高了超声在BCS支架置入术后疗效评估中的应用价值.%Objective To explore the value of vascular enhancement technology (VET) in the evaluation of therapeutic efficacy of stenting for Budd-Chiari syndrome (BCS).Methods Two-dimensional ultrasound,color Doppler and VET were performed on 39 BCS patients with 41 stents,the static and dynamic images of stents and vessels with stents were stored.VET and two-dimensional ultrasound imaging quality of intravascular stent were compared.Patients with stent stenosis found by ultrasound were examined by digital subtraction angiography(DSA).The ranges of stent thrombosis were measured by DSA and VET and the difference was compared.Results VET image quality scores of endovascular stent were higher than those of the two-dimensional ultrasound,the difference was statistically significant.The ranges of stent thrombosis measured by VET were similar to DSA.Conclusions VET can improve the clarity of intravascular stents.VET and color Doppler can enhance the clinical value of ultrasound in the evaluation of therapeutic efficacy of stenting for BCS.

  18. Human epidermal growth factor receptor 3 (HER3) blockade with U3-1287/AMG888 enhances the efficacy of radiation therapy in lung and head and neck carcinoma.

    Science.gov (United States)

    Li, Chunrong; Brand, Toni M; Iida, Mari; Huang, Shyhmin; Armstrong, Eric A; van der Kogel, Albert; Wheeler, Deric L

    2013-09-01

    HER3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In the present study, we investigated the capacity of the HER3 blocking antibody, U3-1287/AMG888, to modulate the in vitro and in vivo radiation response of human squamous cell carcinomas of the lung and head and neck. We screened a battery of cell lines from these tumors for HER3 expression and demonstrated that all cell lines screened exhibited expression of HER3. Importantly, U3-1287/AMG888 treatment could block both basal HER3 activity and radiation induced HER3 activation. Proliferation assays indicated that HER3 blockade could decrease the proliferation of both HNSCC cell line SCC6 and NSCLC cell line H226. Further, we demonstrated that U3-1287/AMG888 can sensitize cells to radiation in clonogenic survival assays, in addition to increasing DNA damage as detected via λ-H2AX immunofluorescence. To determine if U3-1287/AMG888 could enhance radiation sensitivity in vivo we performed tumor growth delay experiments using SCC6, SCC1483, and H226 xenografts. The results of these experiments indicated that the combination of U3-1287/AMG888 and radiation could decrease tumor growth in studies using single or fractionated doses of radiation. Analysis of HER3 expression in tumor samples indicated that radiation treatment activated HER3 in vivo and that U3-1287/AMG888 could abrogate this activation. Immunohistochemistry analysis of SCC6 tumors treated with both U3-1287/AMG888 and a single dose of radiation demonstrated that various cell survival and proliferation markers could be reduced. Collectively our findings suggest that U3-1287/AMG888 in combination with radiation has an impact on cell and tumor growth by increasing DNA damage and cell death. These findings suggest that HER3 may play an important role in response to radiation therapy and blocking its activity in combination with radiation may be of therapeutic benefit in human tumors. PMID:23998444

  19. Teacher Efficacy Measurement and Change.

    Science.gov (United States)

    Guskey, Thomas R.

    Research on the concept of teacher efficacy spans over 20 years, but much remains to be learned. Although precise definitions of the concept have always been problematic, in general, teacher efficacy is defined as teacher's belief or conviction that they can influence how well students learn (T. Guskey and P. Passaro, 1994). Efforts to clarify the…

  20. Reticence, Accuracy and Efficacy

    Science.gov (United States)

    Oreskes, N.; Lewandowsky, S.

    2015-12-01

    James Hansen has cautioned the scientific community against "reticence," by which he means a reluctance to speak in public about the threat of climate change. This may contribute to social inaction, with the result that society fails to respond appropriately to threats that are well understood scientifically. Against this, others have warned against the dangers of "crying wolf," suggesting that reticence protects scientific credibility. We argue that both these positions are missing an important point: that reticence is not only a matter of style but also of substance. In previous work, Bysse et al. (2013) showed that scientific projections of key indicators of climate change have been skewed towards the low end of actual events, suggesting a bias in scientific work. More recently, we have shown that scientific efforts to be responsive to contrarian challenges have led scientists to adopt the terminology of a "pause" or "hiatus" in climate warming, despite the lack of evidence to support such a conclusion (Lewandowsky et al., 2015a. 2015b). In the former case, scientific conservatism has led to under-estimation of climate related changes. In the latter case, the use of misleading terminology has perpetuated scientific misunderstanding and hindered effective communication. Scientific communication should embody two equally important goals: 1) accuracy in communicating scientific information and 2) efficacy in expressing what that information means. Scientists should strive to be neither conservative nor adventurous but to be accurate, and to communicate that accurate information effectively.

  1. Infliximab: Efficacy in psoriasis

    Directory of Open Access Journals (Sweden)

    Shehnaz Arsiwala

    2013-01-01

    Full Text Available Moderate to severe psoriasis often needs to be addressed with standard disease modifying therapies such as methotrexate, cyclosporine, acitretin or ultraviolet radiation, which have their potential benefits and limitations. The tumor necrosis factor-alpha (TNF-α is elevated in psoriatic plaques compared to non lesional skin as well as in the plasma of patients with moderate to severe psoriasis. Infliximab, a TNF-α blocker, has been recommended for the treatment of moderate to severe plaque psoriasis in adults who have failed to respond to these therapies or who cannot tolerate them. Its specific action on the bound and membrane forms of the pro-inflammatory cytokine TNF-α has made it the molecule of choice for obtaining quicker and longer remission in recalcitrant cases. However, the widespread use of infliximab in the Indian subcontinent is limited by its cost. This article reviews the international guidelines for use of infliximab, its dosage patterns, and efficacy in chronic plaque psoriasis, nail psoriasis, erythrodermic psoriasis, and pustular psoriasis as well as Indian experience.

  2. Expressing and responding to self-efficacy in client–social worker interactions

    DEFF Research Database (Denmark)

    Danneris, Sophie; Dall, Tanja

    2016-01-01

    Self-efficacy is a pivotal element when the long-term unemployed are to increase their chances of labour market participation, making the ways in which clients’ beliefs in their capabilities are reflected in the delivery of public employment services particularly relevant. While existing research...... has pointed to the importance of both meetings with social services and self-efficacy for return to work, little knowledge exists on how self-efficacy is managed in these meetings. However, if social workers are to effectively enhance clients’ self-efficacy, knowing that self-efficacy is important is...... worker responses to clients’ expressions can range from supporting to transferring to challenging. Insight into the detailed ways in which self-efficacy is managed in the institutional framework of employment services, we argue, provides a starting point for reflexive consideration on how to develop...

  3. Drug Efficacy Testing in Mice

    OpenAIRE

    Kim, William Y.; Sharpless, Norman E.

    2012-01-01

    The traditional path of drug development passes from in vitro screening and response assessment to validation of drug efficacy in cell line xenografts. While xenografts have their merits, historically, more often than not, they have not served as an accurate predictor of drug efficacy in humans. The refinement and increased availability of genetically engineered mouse models (GEMMs) of cancer has made GEMMs an attractive avenue for the preclinical testing of therapeutic agents. The histopatho...

  4. Enhancing the Efficacy of Antihypertensive Treatment with Pharmacogenomics

    Institute of Scientific and Technical Information of China (English)

    陈慧

    2004-01-01

    @@ In 2003, two newguidelines for hypertensive prevention and management have been provided by American JNC7 and European Society of Hypertension.They advocated that the physician should choose drugs following individualized treatment,which should also be followed by integrative traditional and western medicine.

  5. Enhancing the Efficacy of Antihypertensive Treatrnent with Pharmacogenomics

    Institute of Scientific and Technical Information of China (English)

    陈慧

    2004-01-01

    In 2003, two new guidelines for hypertensive prevention and management have beenprovided by American JNC7 and European Society of Hypertension. They advocated that the physician should choose drugs following individualized treatment , which should also be followed by integrative traditional and western medicine. The emerging field of pharmaeogenomies has the potential to fundamentally change the management of essential hypertension (EH), a common polygenic syndrome characterized by substantial inter-individual variability in drug responsiveness.

  6. Nutlin-3 Enhances Sorafenib Efficacy in Renal Cell Carcinoma

    OpenAIRE

    Vatsyayan, Rit; Singhal, Jyotsana; Nagaprashantha, Lokesh Dalasanur; Awasthi, Sanjay; SINGHAL, SHARAD S.

    2011-01-01

    The renal cell carcinoma (RCC) is one of the top ten cancers in USA. The renal tumors are highly angiogenic and are resistant to conventional interventions, particularly radiotherapy. The advent of multispecific tyrosine kinase inhibitor sorafenib has improved the progression-free survival in RCC, but overall survival in recurrent and metastatic RCC is still a concern that has lead to characterization of combinatorial regimens. Hence, we studied the effect of combination of nutlin-3, an MDM2 ...

  7. Rapamycin-Induced Enhancement of Vaccine Efficacy in Mice

    OpenAIRE

    Jagannath, Chinnaswamy; Bakhru, Pearl

    2012-01-01

    Th1 immunity protects against tuberculosis infection in mice and humans. The widely used BCG vaccine primes CD4 and CD8 T cells through signaling mechanisms from dendritic cells and macrophages. The latter express MHC-II and MHC-I molecules through which peptides from BCG vaccine are presented to CD4 and CD8 T cells, respectively. Since BCG sequesters within a phagosome that does not fuse with lysosomes, generation of peptides within antigen-presenting cells infected with BCG occurs with redu...

  8. 两种分割模式下甘露聚糖肽联合放疗对Lewis肺癌的生长抑制作用%Mannatide enhances the efficacy of fractionated and unfractionated radiotherapy in mice bearing Lewis lung cancer

    Institute of Scientific and Technical Information of China (English)

    樊锐太; 胡勇; 刘俊启; 张晶晶; 宋锐; 顾浩

    2011-01-01

    Objective To investigate the effect of mannatide injection (MI) in enhancing the efficacy of radiotherapy in two therapeutic schedules in mice bearing Lewis lung cancer. Methods C57BL/6 mice bearing Lewis lung cancer xenograft were assigned randomly into control group, fractionated schedule (FS) group, nonfractionated schedule (NFS) group, MI group, FS+MI group, and NFS+MI group (n=10). MI (4.5 mg/kg) or saline was given intraperitoneally for 14 consecutive days in the corresponding groups. Radiation with 8 MeV electron beam was delivered in a single 4 Gy dose in NFS and in 4 fractions (total dose 4 Gy) in FS. Tumor inhibition rate and the spleen and thymus index were calculated after the treatments. Results MI significantly enhanced the efficacy of radiotherapy with a tumor inhibition rate reaching 70% in FS+MI group (P<0.01). FS resulted in a significantly higher tumor inhibition rate than NFS (P< 0.05), but the rates were comparable between FS+MI and NFS+MI groups. The spleen index and thymus indices were significantly higher in FS+MI and NFS+MI groups than in FS and NFS groups (P<0.05). Conclusion MI can enhance the efficacy of radiotherapy with different therapeutic schedules in mice bear Lewis lung cancer, and MI plus fractionated radiation produces the optimal effect.%目的 探讨两种放疗分割模式下甘露聚糖肽注射液(MI)对Lewis肺癌小鼠移植瘤的生长抑制作用.方法 建立C57BL/6小鼠Lewis肺癌实体型,选取C57BL/6小鼠60只(右前肢腋部的肿瘤直径大小约6mm),随机分为空白对照组,分割照射组(FS),不分割照射组(NFS),MI组,分割照射联合MI组(FS+MI),不分割照射联合MI(NFS+MI)6组.给药组小鼠均腹腔注射MI4.5 mg/kg,连续14d,余各组均腹腔注射等体积生理盐水;照射组小鼠经8MeV电子线照射治疗,其中不分割方案各组小鼠接受4Gy/次,照射1次,分割方案各组小鼠给予1Gy/次,照射4次,1次/d.观察各组小鼠一般状况,剥离肿瘤,称取质量,计算

  9. Self-Efficacy: Conditioning the Entrepreneurial Mindset

    DEFF Research Database (Denmark)

    Neergaard, Helle; Mauer, René; Kirketerp Linstad, Anne

    2009-01-01

    Research that has sought to identify the underlying determinants of self-efficacy is sparse. This chapter seeks to identify antecedents of entrepreneurial self-efficacy and the processes that produce and reinforce self-efficacy. It seeks to broaden our understanding of the self-efficacy concept...

  10. Efficacy monitoring of in situ fuel bioremediation

    International Nuclear Information System (INIS)

    The wide-scale, multiple-purpose use of fossil fuels throughout the industrialized world has resulted in the inadvertent contamination of myriad environments. Given the scope and magnitude of these environmental contamination problems, bioremediation often represents the only practical and economically feasible solution. This is especially true when depth of contamination, magnitude of the problem, and nature of contaminated material preclude other remedial actions, short of the no-response alternative. From the perspective, the effective, safe and scientifically valid use of in situ bioremediation technologies requires cost-efficient and effective implementation strategies in combination with unequivocal approaches for monitoring efficacy of performance. Accordingly, with support from the SERDP program, the authors are field-testing advanced in situ bioremediation strategies and new approaches in efficacy monitoring that employ techniques instable carbon and nitrogen isotope biogeochemistry. One field demonstration has been initiated at the NEX site in Port Hueneme, CA (US Navy's National Test Site). The objectives are: (1) to use stable isotopes as a biogeochemical monitoring tool for in situ bioremediation of refined petroleum (i.e., BTEX), and (2) to use vertical groundwater circulation technology to effect in situ chemical containment and enhanced in situ bioremediation

  11. Enteral feeding pumps: efficacy, safety, and patient acceptability

    OpenAIRE

    White H; King L

    2014-01-01

    Helen White, Linsey King Nutrition and Dietetic Group, School of Health and Wellbeing, Faculty Health and Social Science, Leeds Metropolitan University, Leeds, United Kingdom Abstract: Enteral feeding is a long established practice across pediatric and adult populations, to enhance nutritional intake and prevent malnutrition. Despite recognition of the importance of nutrition within the modern health agenda, evaluation of the efficacy of how such feeds are delivered is more limited. The accu...

  12. Plum-blossom needle tapping enhances the efficacy of aminolevulinic acid-based photodynamic therapy for actinic keratosis, basal cell carcinoma and squamous cell carcinoma%梅花针叩刺增强氨基酮戊酸光动力治疗光线性角化病、基底细胞癌、鳞状细胞癌的研究

    Institute of Scientific and Technical Information of China (English)

    王佩茹; 张玲琳; 周忠霞; 魏茗蕾; 石磊; 吉杰; 杨德刚; 张国龙; 王秀丽

    2015-01-01

    pretreated with plum-blossom needle tapping followed by ALA-PDT,and the control group by ALA-PDT alone.Results The complete remission rate of actinic keratosis after the first session of treatment was significantly higher in the combination group than in the control group (grade 1 lesions,12/12 vs.10/14; grade 2 lesions,79.5% (31/39) vs.57.9% (22/38); grade 3 lesions,36.6% (15/41) vs.17.0% (7/41),all P < 0.05).The number of treatment sessions required for the complete remission of actinic keratosis and squamous cell carcinoma in situ lesions measuring more than 0.3 mm in thickness was significantly reduced in the combination group compared with the control group.On average,1.9 sessions of treatment were required for the complete remission of grade 3 lesions of actinic keratosis in the combination group,compared to 2.6 sessions in the control group.Plum-blossom needle tapping also enhanced the efficacy of ALA-PDT for nodular basal cell carcinoma.Further more,plum-blossom needle tapping did not aggravate pain in patients during the treatment.Conclusion Plum-blossom needle tapping can enhance the efficacy of ALA-PDT for actinic keratosis,basal cell carcinoma and squamous cell carcinoma,with no increase in adverse reactions.

  13. Application of vascular enhancement technology in the diagnosis of Budd-Chiari syndrome and evaluation of the therapeutic efficacy of interventional therapy%超声血管增强技术在布-加综合征诊断及介入治疗疗效评估中的应用

    Institute of Scientific and Technical Information of China (English)

    王兴田; 朱巧英; 王荣; 崔建华; 祖茂衡

    2011-01-01

    目的 探讨超声血管增强技术(VET)在布-加综合征(BCS)诊断及介入治疗疗效评估中的应用价值.方法 应用二维超声、彩色多普勒及VET对93例BCS患者介入术前肝内血管及下腔静脉进行系统检测,存储上述血管静态及动态图像,术后同法检测治疗血管.比较术前被检血管及术后治疗血管二维超声与VET图像的清晰度,并比较经DSA证实的病变血管二维超声及VET诊断符合率.结果 术前613条受检血管,二维超声显示清晰440条,VET显示清晰533条,两者差异有统计学意义(P<0.05);VET尚显示了37条二维超声不可见的肝内细小交通支.以DSA为金标准,146条病变血管二维超声及VET诊断符合率分别为 69.2%、92.5%,差异有统计学意义(P<0.05).103条治疗血管,术后二维超声清晰显示81条,VET清晰显示95条,两者差异有统计学意义(P<0.05).结论 VET可改善肝内血管、下腔静脉及血管内支架的清晰度,与彩色多普勒相结合,提高了超声在BCS诊断及介入治疗疗效评估中的应用价值.%Objective To explore the value of the application of vascular enhancement technology (VET) in the diagnosis of Budd-Chiari syndrome (BCS) and the evaluation of the therapeutic efficacy of interventional therapy.Methods B-mode ultrasound,color Doppler and VET were performed on 93 patients with BCS for the systematic detection of intrahepatic vessels and the inferior vena cava (IVC),with the static and dynamic images of these vessels stored prior to interventional therapy.Subsequent to the operation,the same procedures were repeated on the vessels concerned and the images were recorded.The definitions of B-mode and VET images of the detected vessels were compared by two sonography experts.Regarding DSA as standard,the diagnostic accordance rate of VET and B-mode imaging of the diseased vessels was compared.Results Of the 613 vessels detected prior to intervention therapy,440 vessels images were distinct by B

  14. Goal Setting and Self-Efficacy among Delinquent, At-Risk and Not At-Risk Adolescents

    Science.gov (United States)

    Carroll, Annemaree; Gordon, Kellie; Haynes, Michele; Houghton, Stephen

    2013-01-01

    Setting clear achievable goals that enhance self-efficacy and reputational status directs the energies of adolescents into socially conforming or non-conforming activities. This present study investigates the characteristics and relationships between goal setting and self-efficacy among a matched sample of 88 delinquent (18% female), 97 at-risk…

  15. Effects of the Badge Mechanism on Self-Efficacy and Learning Performance in a Game-Based English Learning Environment

    Science.gov (United States)

    Yang, Jie Chi; Quadir, Benazir; Chen, Nian-Shing

    2016-01-01

    A growing number of studies have been conducted on digital game-based learning (DGBL). However, there has been a lack of attention paid to individuals' self-efficacy and learning performance in the implementation of DGBL. This study therefore investigated how the badge mechanism in DGBL enhanced users' self-efficacy in the subject domain of…

  16. Control efficacy of complex networks

    Science.gov (United States)

    Gao, Xin-Dong; Wang, Wen-Xu; Lai, Ying-Cheng

    2016-06-01

    Controlling complex networks has become a forefront research area in network science and engineering. Recent efforts have led to theoretical frameworks of controllability to fully control a network through steering a minimum set of driver nodes. However, in realistic situations not every node is accessible or can be externally driven, raising the fundamental issue of control efficacy: if driving signals are applied to an arbitrary subset of nodes, how many other nodes can be controlled? We develop a framework to determine the control efficacy for undirected networks of arbitrary topology. Mathematically, based on non-singular transformation, we prove a theorem to determine rigorously the control efficacy of the network and to identify the nodes that can be controlled for any given driver nodes. Physically, we develop the picture of diffusion that views the control process as a signal diffused from input signals to the set of controllable nodes. The combination of mathematical theory and physical reasoning allows us not only to determine the control efficacy for model complex networks and a large number of empirical networks, but also to uncover phenomena in network control, e.g., hub nodes in general possess lower control centrality than an average node in undirected networks.

  17. Infant Care Self-Efficacy.

    Science.gov (United States)

    Froman, Robin D.

    The Infant Care Survey (ICS) was developed to measure new mothers' confidence in their knowledge and skills regarding the care of babies under one year of age. One potential use of this test would be the identification of groups at high risk for health problems or for avoiding medical care. Self-efficacy was an important construct in the…

  18. A conceptual model of referee efficacy

    Directory of Open Access Journals (Sweden)

    Félix eGuillén

    2011-02-01

    Full Text Available This paper presents a conceptual model of referee efficacy, defines the concept, proposes sources of referee specific efficacy information, and suggests consequences of having high or low referee efficacy. Referee efficacy is defined as the extent to which referees believe they have the capacity to perform successfully in their job. Referee efficacy beliefs are hypothesized to be influenced by mastery experiences, referee knowledge/education, support from significant others, physical/mental preparedness, environmental comfort, and perceived anxiety. In turn, referee efficacy beliefs are hypothesized to influence referee performance, referee stress, athlete rule violations, athlete satisfaction, and co-referee satisfaction.

  19. Learning to fit in: an exploratory study of general perceived self efficacy in selected refugee groups.

    Science.gov (United States)

    Sulaiman-Hill, Cheryl M R; Thompson, Sandra C

    2013-02-01

    As self efficacy beliefs help determine an individual's response to challenging situations, we explored the impact of the refugee experience on efficacy beliefs and their contribution to resettlement. General self efficacy (GSE) was assessed in 186 resettled Afghan and Kurdish refugees against a range of personal and temporal variables. Although no differences in GSE in relation to temporal factors were noted, significant relationships between self efficacy, lower psychological distress and higher subjective well being were evident. The findings suggest that GSE, because of its positive association with mental health and well being, is a variable worthy of further examination in refugees. In addition to ensuring a supportive environment for learning English, proactive employment strategies should be encouraged. Further research examining the use of successful refugee role models to promote self efficacy, enhance motivation for learning and ensure newly arrived refugees view resettlement as a challenge, rather than a threat, is recommended. PMID:22086715

  20. Cancer survivors’ self-efficacy to self-manage in the year following primary treatment

    OpenAIRE

    Foster, Claire; Breckons, Matthew; Cotterell, P.; D. Barbosa; Calman, Lynn; Corner, Jessica; Fenlon, Deborah; Foster, R.; Grimmett, Chloe; Richardson, Alison; Smith, P.W.

    2014-01-01

    PURPOSE: Cancer survivors are increasingly expected to manage the consequences of cancer and its treatment for themselves. There is evidence that self-efficacy is important for successful self-management and that this can be enhanced with support. The purpose of this study was to assess self-efficacy to manage problems in the year following primary treatment. METHODS: This cross-sectional online survey included cancer survivors who had completed their treatment within the past 1...

  1. Student teacher self-efficacy and student perceptions of assessment in competence-based education

    OpenAIRE

    van Dinther, Martinus

    2015-01-01

    Teacher self-efficacy or “teachers’ beliefs in their ability to havea positive effect on student learning” (Ashton, 1985, p. 142), has beenevidenced as affecting student achievement, motivation and attitude towards school. Therefore, enhancing student teacher self-efficacy should be high on the agenda of teacher educational programmes. The core goal ofthis doctoral thesis is to provide evidence for how assessment in a competence-based teacher education programme influences student teacher sel...

  2. Microwave ablation of liver metastases guided by contrast-enhanced ultrasound

    DEFF Research Database (Denmark)

    Lorentzen, T; Skjoldbye, B O; Nolsoe, C P

    2011-01-01

    The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS).......The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS)....

  3. Pre-Service Teachers' Mathematics Self-Efficacy and Mathematics Teaching Self-Efficacy

    Science.gov (United States)

    Zuya, Habila Elisha; Kwalat, Simon Kevin; Attah, Bala Galle

    2016-01-01

    Pre-service mathematics teachers' mathematics self-efficacy and mathematics teaching self-efficacy were investigated in this study. The purpose was to determine the confidence levels of their self-efficacy in mathematics and mathematics teaching. Also, the study was aimed at finding whether their mathematics self-efficacy and teaching…

  4. Preclinical safety and antitumor efficacy of insulin combined with irradiation

    International Nuclear Information System (INIS)

    Background and purpose: We have previously reported that insulin significantly enhances tumor oxygenation (pO2) and increases radiation-induced tumor regrowth delay in experimental models. Considering the large radiosensitizing effect, clinical trials might be envisioned. The aim of the present pre-clinical study was to obtain a more complete set of safety and efficacy data which would further justify the commencement of such clinical trials. Material and methods: Toxicity on normal (early and late-responding) tissues was measured by the intestinal crypt regeneration assay and the late leg contracture assay. Efficacy in terms of enhancement of pO2 (measured by in vivo EPR oximetry) and increase in radiation-induced tumor regrowth delay was evaluated with a dose-response study on mice bearing FSaII fibrosarcoma. Results: The effect on regrowth delay was directly correlated with the effect on the tumor pO2, with a maximal effect using 400 mU kg-1 insulin. Importantly, there was no increase in the radiation toxicity for normal tissues. Finally, we found that the hypoglycaemia induced by insulin can be corrected by simultaneous glucose infusion without modification of efficacy. Conclusion: Insulin here demonstrated a therapeutic gain and a lack of toxicity to normal tissues. The results of this study fully justify further larger preclinical assays such as the use of fractionated irradiation and a tumor control dose assay, before determining the utility of insulin as a radiosensitizer for human patients in the clinic

  5. The Influence of Climate Change Efficacy Messages and Efficacy Beliefs on Intended Political Participation

    Science.gov (United States)

    Hart, P. Sol; Feldman, Lauren

    2016-01-01

    Using an online survey experiment with a national sample, this study examined how changing the type and valence of efficacy information in news stories discussing global climate change may impact intended political participation through the mediators of perceived internal, external, and response efficacy. Overall, the results revealed that after a single exposure to a news story, stories including positive internal efficacy content increased perceived internal efficacy, while stories including negative external efficacy content lowered perceived external efficacy. There were limited impacts of other types of efficacy content on perceived efficacy. Perceived internal, external, and response efficacy all offered unique, positive associations with intentions to engage in climate change-related political participation. The results suggest that news stories including positive internal efficacy information in particular have the potential to increase public engagement around climate change. The implications for science communication are discussed. PMID:27487117

  6. Study and Evaluation of the Therapeutic Efficacy of Phlebothrombosis of Lower Extremity in Acute Stage with Vascular Enhancement Technology%超声血管增强技术对下肢静脉血栓急性期治疗效果的评估价值研究

    Institute of Scientific and Technical Information of China (English)

    唐水娟; 刘丽; 李文彬; 熊石龙

    2013-01-01

    目的 探讨超声血管增强技术(VET)对下肢深静脉血栓急性期治疗效果的评估价值.方法 选取2009年12月-2010年9月本院诊断为下肢深静脉血栓急性期并进行治疗的患者21例,应用VET及彩色多普勒(CDFI)于治疗前后检查下肢深静脉,比较治疗前后血栓情况、血流再通率,分析下肢深静脉常见部位.结果 共显示91条下肢深静脉血栓形成,其中完全闭塞16条,CDFI显示无血流信号,VET显示管腔内充满均质性低回声;不完全闭塞75条,CDFI及VET均显示管腔内出现不同程度的充盈缺损.经溶栓治疗后,完全闭塞者VET显示10例出现再通现象,再通率为62.5%,高于CDFI的43.8%(7/16),差异有统计学意义(χ2=13.053,P=0.021).不同类型下肢深静脉血栓检出率比较,差异有统计学意义(χ2=14.056,P=0.014),其中以股静脉段最多见(χ2=23.078,P=0.004).左下肢检出率为61.5%(56/91)高于右下肢的38.5%(35/91),差异有统计学意义(χ2=9.692,P=0.002).12条存在小腿深静脉血栓患者,VET检出率为83.3%(10/12),明显高于CDFI的66.7%(8/12),差异有统计学意义(χ2=19.702,P=0.003).结论 VET能提高血管血栓显示能力及血管显示灵敏度,较好评估下肢深静脉血栓急性期患者治疗效果及小腿深部静脉血栓显示率.%Objective To study and evaluate the therapeutic efficacy of phlebothrombosis of lower extremity in acute stage with vascular enhancement technology ( VET ) . Methods A total of 21 patients diagnosed as phlebothrombosis of lower extremity in acute stage and treated during the period from December 2009 to September 2010 were selected. Patients' deep veins of lower limbs before and after treatment were examed by VET and color doppler flow imaging ( CDFI ), the area of the thromb and the recanalization rate in the thromb before and after treatment were compared, the common location of thromb in deep veins of lower limb was analyzed. Results There were 91 phlebothrombosis of lower

  7. Strategies to improve the efficacy of radioimmunotherapy: Radiobiologic aspects

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate methods of improving the therapeutic index (dose to tumor/dose to normal organs) and, hence, the efficacy of radioimmunotherapy (RIT). One method investigated was to increase the biologic response for a given radiation dose to tumor. To enhance the biologic efficacy of the dose, initial studies focused on first understanding the radiobiology of RIT irradiation and determining what role factors, such as radiation repair, repopulation, and redistribution, play in determining RIT response. In vitro studies using 4 colon carcinoma cell lines have compared the radiobiologic efficacy of low dose-rate irradiation delivered by Yttrium-90 (Y-90) with conventional high dose-rate external beam irradiation (XRT). Results suggested that one factor which determined a cell's sensitivity to Y-90 irradiation was its ability to repair radiation sublethal damage. In vivo studies demonstrated that those cell lines which were more sensitive to Y-90 irradiation in vitro were also more sensitive to RIT in vivo. For a more radioresistant line, WiDr, RIT was approximately two-fold less effective than an equivalent dose of single fraction XRT, while for a more radiosensitive line, LS174T, RIT was approximately as effective as an equivalent dose of single fraction XRT. Therefore, a tumor's response to RIT in vivo appeared to be, in part, dependent on the tumor cell's ability to repair radiation damage. Finally, studies investigated strategies at enhancing the biologic efficacy of RIT irradiation by combining RIT with chemotherapy agents that can potentially inhibit radiation repair. Agents, such as 5-fluorouracil, appeared to be synergistic with RIT irradiation n vitro and may therefore prove promising in improving the therapeutic index of RIT

  8. Comparison of Nitrogen Fertilizers, Induce and Zinc Addition on Glyphosate Efficacy on Three Different Weed Species.

    Directory of Open Access Journals (Sweden)

    Hussein F. Abouziena

    2014-05-01

    Full Text Available Herbicides are often tank-mixed with fertilizers to save time, labour, energy, and equipment costs. However addition of some additives with glyphosate may result in reducing glyphosate efficacy. Therefore we evaluated the potential of three nitrogen sources (ammonium sulphate (AMS at 2 or 4% w/v, ammonium nitrate (AN at 1 or 2% w/v, urea at 1 or 2 % w/v, nonionic adjuvant (Induce at 0.05% v/v and Zn at 250 g Zn/ha (1321 ppm to enhance glyphosate efficacy on pig weed (Amaranthus retroflexus L., crowfoot grass (Dactyloctenium egyptium L. and yellow nutsedge (Cyperus esculentus L. under greenhouse conditions. The results indicated that there were variations in susceptibility of the three weeds to glyphosate+adjuvant treatments. Addition of AN at 2% reduced the efficacy of glyphosate on crowfoot grass. There was an antagonistic effect between glyphosate herbicide and Zn; the phytotoxic effect of glyphosate on the three weeds was less than 50 %. Zinc tank-mixed with glyphosate resulted in a greater number of tubers and shoots per plant than the untreatedol. Addition of AN or urea at 2% reduced glyphosate efficacy by about 2.3 and 9 %, respectively, relative to their addition at 1%. Tankmixes of urea (1%, AN (1%, AMS (2% and Induce adjuvant (0.05% generally enhanced the efficacy of glyphosate (0.85 kg/ha, whereas the addition of Zn, as zinc sulphate, to glyphosate sprays adversely affected herbicide efficacy.

  9. Tip enhancement

    CERN Document Server

    Kawata, Satoshi

    2007-01-01

    This book discusses the recent advances in the area of near-field Raman scattering, mainly focusing on tip-enhanced and surface-enhanced Raman scattering. Some of the key features covered here are the optical structuring and manipulations, single molecule sensitivity, analysis of single-walled carbon nanotubes, and analytic applications in chemistry, biology and material sciences. This book also discusses the plasmonic materials for better enhancement, and optical antennas. Further, near-field microscopy based on second harmonic generation is also discussed. Chapters have been written by some of the leading scientists in this field, who present some of their recent work in this field.·Near-field Raman scattering·Tip-enhanced Raman spectroscopy·Surface-enhanced Raman spectroscopy·Nano-photonics·Nanoanalysis of Physical, chemical and biological materials beyond the diffraction limits·Single molecule detection

  10. Self-Efficacy as a Positive Youth Development Construct: A Conceptual Review

    Directory of Open Access Journals (Sweden)

    Sandra K. M. Tsang

    2012-01-01

    Full Text Available Self-efficacy denotes people's beliefs about their ability to perform in different situations. It functions as a multilevel and multifaceted set of beliefs that influence how people feel, think, motivate themselves, and behave during various tasks. Self-efficacy beliefs are informed by enactive attainment, vicarious experience, imaginal experiences, and social persuasion as well as physical and emotional states. These beliefs are mediated by cognitive, motivational, affective, and selection processes to generate actual performance. Self-efficacy development is closely intertwined with a person's experiences, competencies, and developmental tasks in different domains at different stages in life. This paper reviews the literature to outline the definition and theoretical conceptualizations of the construct originally devised by Bandura that have flourished since the 1990s. Drawing from the studies of the construct to assess self-efficacy, and to inform positive youth development, the paper will present the determinants of the development of self-efficacy beliefs and identify the connection between self-efficacy and adolescent developmental outcomes. The paper will conclude with strategies to enhance youth self-efficacy and proposals for future research directions.

  11. Self-efficacy as a positive youth development construct: a conceptual review.

    Science.gov (United States)

    Tsang, Sandra K M; Hui, Eadaoin K P; Law, Bella C M

    2012-01-01

    Self-efficacy denotes people's beliefs about their ability to perform in different situations. It functions as a multilevel and multifaceted set of beliefs that influence how people feel, think, motivate themselves, and behave during various tasks. Self-efficacy beliefs are informed by enactive attainment, vicarious experience, imaginal experiences, and social persuasion as well as physical and emotional states. These beliefs are mediated by cognitive, motivational, affective, and selection processes to generate actual performance. Self-efficacy development is closely intertwined with a person's experiences, competencies, and developmental tasks in different domains at different stages in life. This paper reviews the literature to outline the definition and theoretical conceptualizations of the construct originally devised by Bandura that have flourished since the 1990s. Drawing from the studies of the construct to assess self-efficacy, and to inform positive youth development, the paper will present the determinants of the development of self-efficacy beliefs and identify the connection between self-efficacy and adolescent developmental outcomes. The paper will conclude with strategies to enhance youth self-efficacy and proposals for future research directions. PMID:22645423

  12. The Effect of Mathematics Self-Efficacy on Anxiety of Teaching Mathematics

    Directory of Open Access Journals (Sweden)

    Alattin URAL

    2015-04-01

    Full Text Available The aim of the study is to investigate the effect of mathematics self-efficacy belief on anxiety of teaching mathematics. The participants of the study consist of 42 mathematics teacher candidates in the Department of Mathematics Education, Faculty of Education. The scale of mathematics self-efficacy, developed by Umay (2001, and the scale of mathematics teaching anxiety, developed by Peker (2006, was enrolled as measurement tools. Pearson correlation was used for the correlation between teacher candidates’ average points from the both scales. The results revealed that there was a significant and negative correlation mathematics self-efficacy beliefs and anxiety of teaching mathematics. This result means that the students’ mathematics teaching anxiety decreases as their mathematics self-efficacy beliefs increase. On the other hand, it was seen that mathematics self-efficacy belief explains 35% of the variance in teaching mathematics anxiety. Besides, it was determined that mathematics teacher candidates’ mathematics teaching anxiety was at low level, and mathematics efficacy beliefs are at high level. Mathematics self-efficacy refers to the belief or perception that one is capable of organizing and executing the actions necessary to succeed at a given mathematical task. For this aim, their knowledge and abilities relating mathematical concepts and also their confidences about their mathematical abilities must be enhanced.

  13. Physical activity intervention effects on perceived stress in working mothers: the role of self-efficacy.

    Science.gov (United States)

    Mailey, Emily L; McAuley, Edward

    2014-01-01

    Working mothers often report elevated stress, and efforts to improve their coping resources are needed to buffer the detrimental effects of stress on health. This study examined the impact of changes in physical activity, self-efficacy, and self-regulation across the course of a brief intervention on subsequent levels of stress in working mothers. Participants (N = 141) were randomly assigned to an intervention or control condition (2:1 ratio). The intervention was conducted in Illinois between March 2011 and January 2012 and consisted of two group-mediated workshop sessions with content based on social cognitive theory. Participants completed measures of physical activity, self-efficacy, self-regulation, and perceived stress at baseline, immediately postintervention, and 6-month follow-up. Stress levels declined across the 6-month period in both groups. Changes in stress were negatively associated with changes in self-efficacy and self-regulation among intervention participants only. Regression analyses revealed the intervention elicited short-term increases in physical activity, self-efficacy, and self-regulation, but only changes in self-efficacy predicted perceived stress at 6-month follow-up. These results suggest that enhancing self-efficacy is likely to improve working mothers' perceived capabilities to cope with stressors in their lives. Future interventions should continue to focus on increasing self-efficacy to promote improvements in physical activity and psychological well-being in this population. PMID:24964227

  14. Breastfeeding self-efficacy among adolescent mothers

    OpenAIRE

    Renata de Lima Bizerra; Jéssica Pinheiro Carnaúba; Anne Fayma Lopes Chaves; Rebeca Silveira Rocha; Hérica Cristina Alves de Vasconcelos; Mônica Oliveira Batista Oriá

    2015-01-01

    The objective of the study was to assess breastfeeding self-efficacy among lactating adolescents. A quantitative study involving 172 lactating adolescents, conducted in 14 Basic Health Units in the northeast cities of Brazil. For data collection, we used a form and the Breastfeeding Self-Efficacy Scale – Short Form. Data were analyzed with a statistical software. Results showed high breastfeeding self-efficacy (84%), with more adherence to the items: “Ensure that my baby is properly latched o...

  15. Medication Treatment Efficacy and Chronic Orofacial Pain.

    Science.gov (United States)

    Clark, Glenn T; Padilla, Mariela; Dionne, Raymond

    2016-08-01

    Chronic pain in the orofacial region has always been a vexing problem for dentists to diagnose and treat effectively. For trigeminal neuropathic pain, there are 3 medications (gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors) to use plus topical anesthetics that have therapeutic efficacy. For chronic daily headaches (often migraine in origin), 3 prophylactic medications have reasonable therapeutic efficacy (β-blockers, tricyclic antidepressants, and antiepileptic drugs). The 3 Food and Drug Administration-approved drugs for fibromyalgia (pregabalin, duloxetine, and milnacipran) are not robust, with poor efficacy. For osteroarthritis, nonsteroidal anti-inflammatory drugs have therapeutic efficacy and when gastritis contraindicates them, corticosteriod injections are helpful. PMID:27475515

  16. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    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

  17. Cognitive Restructuring in the Treatment of Social Phobia: Efficacy and Mode of Action.

    Science.gov (United States)

    Taylor, Steven; Woody, Sheila; Koch, William J.; McLean, Peter; Paterson, Randy J.; Anderson, Kent W.

    1997-01-01

    Examines whether cognitive restructuring (CR) contributes to treatment efficacy and investigates its mode of action for therapeutic effects. Results, based on 60 persons with generalized social phobia, indicate that CR reduced social phobia and negative social cognitions and increased positive cognitions. CR did not enhance the effects of…

  18. Efficacy of Pseudomonas fluorescens for biocontrol of Escherichia coli 0157:H7 on spinach

    Science.gov (United States)

    Control of foodborne pathogens on leafy green vegetables is crucial for consumer food safety. Biocontrol microbes may inhibit or suppress foodborne pathogen growth and enhance existing post-harvest intervention controls. The efficacy of Pseudomonas fluorescens for biocontrol of Escherichia coli O157...

  19. Efficacy of 'Tailored Physical Activity' in reducing sickness absence among health care workers

    DEFF Research Database (Denmark)

    Nygaard Andersen, Lotte; Juul-Kristensen, Birgit; Roessler, Kirsten Kaya; Herborg, Lene Gram; Sørensen, Thomas Lund; Søgaard, Karen

    2013-01-01

    Health care workers have high physical work demands, involving patient handling and manual work tasks. A strategy for prevention of work-related musculoskeletal disorders can enhance the physical capacity of the health care worker. The aim of this study is to evaluate the efficacy of 'Tailored...... Physical Activity' for health care workers in the Sonderborg Municipality....

  20. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    Vogt, Liffert; Waanders, Fernke; Boornsma, Frans; de Zeeuw, Dick; Navis, Gerjan

    2008-01-01

    There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these intervention

  1. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    L. Vogt (Liffert); F. Waanders (Femke); F. Boomsma (Frans); D. de Zeeuw (Dick); G. Navis (Gerjan)

    2008-01-01

    textabstractThere is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these

  2. Clinical efficacy of nebulized drugs

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    1994-01-01

    nebulized aerosol during expiration. In a subsequent study of 23 young children unresponsive to beta2-agonist therapy, nebulized budesonide was without demonstrable effect. Recently, a study of 31 young children with steroid-dependent asthma demonstrated a significant improvement from continuous......-group of children should be treated as asthmatics. The dose of topical steroids is critical as opposed to that of beta2-agonists which are often administered in doses well above the minimal effective dose. Budesonide suspension has proven its efficacy in adults in a study of 21 patients with asthma treated...... with budesonide suspension delivered from a nebulizer activated during inspiration versus metered dose inhalation (MDI) via a large-volume spacer. Nebulized in this manner the suspension exhibited a dose-dependent effect, apparently equipotent to the MDI administration as evaluated from daily peak...

  3. Against Motivational Efficacy of Beliefs

    Directory of Open Access Journals (Sweden)

    Seungbae Park

    2015-07-01

    Full Text Available Danielle Bromwich (2010 argues that a belief is motivationally efficacious in that, other things being equal, it disposes an agent to answer a question in accordance with that belief. I reply that what we are disposed to do is largely determined by our genes, whereas what we believe is largely determined by stimuli from the environment. We have a standing and default disposition to answer questions honestly, ceteris paribus, even before we are exposed to environmental stimuli. Since this standing and default disposition is innate, and our beliefs have their source in environmental stimuli, our beliefs cannot be the source of the disposition. Moreover, a recent finding in neuroscience suggests that motivation is extrinsic to belief.

  4. Postoperative enhancement

    International Nuclear Information System (INIS)

    The use of contrast agents in MR imaging and CT was compared in the postoperative state in a clinical series and an animal model and was found to vary in two ways. First, gadolinium appeared to be more sensitive than iodinated contrast agent in CT. Specifically, enhancement was noted earlier within the 1st week and later after several months than enhancement with CT. Second, because of the evolution of hemoglobin breakdown products, MR images became increasingly more difficult to interpret after a few days due to residual blood at the operative site. With CT, the visualization of blood diminished with time. In conclusion, the temporal evolution of contrast enhancement in MR imaging and CT is roughly parallel, although it may be even more important in MR to image as early as clinically possible in the postoperative state. Conversely, in the long-term postoperative state, residual normal postoperative enhancement can be seen with contrast-enhanced MR imaging when these changes will no longer be visible with contrast-enhanced CT

  5. Collective Efficacy Beliefs in Student Work Teams: Relation to Self-Efficacy, Cohesion, and Performance

    Science.gov (United States)

    Lent, Robert W.; Schmidt, Janet; Schmidt, Linda

    2006-01-01

    A measure of collective efficacy was developed and administered to undergraduates working in project teams in engineering courses. Findings in each of two samples revealed that the measure contained a single factor and was related to ratings of team cohesion and personal efficacy. Collective efficacy was also found to relate to indicators of team…

  6. Effects of cognitive and experiential group therapy on self-efficacy and perceptions of employability of chemically dependent women.

    Science.gov (United States)

    Washington, O

    1999-01-01

    This quasi-experimental study assessed effects of cognitive and experiential group therapy on self-efficacy and perceptions of employability for 52 chemically dependent adult women. The sample was 98% African American. Therapy consisted of six 90-min group sessions held twice weekly. The participants were pre- and posttested with the Self-Efficacy Scale (M. Sherer et al., 1982) and the Ghiselli Self-Description Inventory (E. E. Ghiselli, 1975). After the intervention, the cognitive group had significantly higher levels than the experiential group of social self-efficacy and need for self-actualization, an indicator of aspiration for employment. General self-efficacy and decisiveness, indicators of employability, significantly increased over time for both groups. Interventions to enhance people's belief in their ability to successfully perform tasks and control outcomes, promote personal growth, teach responsibility, and enhance self-awareness could be used to develop employability skills that reduce recidivism. PMID:10633639

  7. Development of Physics Self-Efficacy Scale

    Science.gov (United States)

    Çalişkan, Serap; Selçuk, Gamze S.; Erol, Mustafa

    2007-04-01

    In this article, we describe development of a Physics Self-Efficacy Scale (PSES) that is a self-administered measure to assess physics self-efficacy beliefs regarding one's ability to successfully perform physics tasks in physics classroom. The scale is initially composed of 56 items prepared following a brief scrutiny of relating literature on self-efficacy. It was initially administered 30 physics teacher candidates and was also examined by 6 experts of physics education, then ambiguous or incomprehensible 6 items were dismissed. This PSES was tested on 558 undergraduate students all completed fundamental physics courses. Cronbach's Alpha reliability coefficient of the PSES was calculated as 0.94. The final version of the PSES contained 30 items with 5 dimensions namely, 1. Self-efficacy towards solving physics problems, 2. Self-efficacy towards physics laboratory, 3. Self-efficacy towards learning physics, 4. Self-efficacy towards application of physics knowledge and 5. Self-efficacy towards memorizing physics knowledge.

  8. Impact of Teacher Preparation upon Teacher Efficacy

    Science.gov (United States)

    Redmon, Robert J.

    2007-01-01

    A cohort of students in a teacher preparation program completed questionnaires measuring their feelings of teacher self efficacy at three points in the program. Results suggest that pre-service teachers' feelings of self efficacy do improve as a result of their participation in such programs. (Contains 1 figure and 1 table. Teacher Efficacy…

  9. Speech enhancement

    CERN Document Server

    Benesty, Jacob; Chen, Jingdong

    2006-01-01

    We live in a noisy world! In all applications (telecommunications, hands-free communications, recording, human-machine interfaces, etc.) that require at least one microphone, the signal of interest is usually contaminated by noise and reverberation. As a result, the microphone signal has to be ""cleaned"" with digital signal processing tools before it is played out, transmitted, or stored.This book is about speech enhancement. Different well-known and state-of-the-art methods for noise reduction, with one or multiple microphones, are discussed. By speech enhancement, we mean not only noise red

  10. LASIK enhancements.

    Science.gov (United States)

    Durrie, D S; Vande Garde, T L

    2000-01-01

    As the field of refractive surgery continues to evolve, an increasing number of surgical options are available for LASIK enhancements. Nonetheless, older methods such as AK continue to play an important role in enhancement procedures. Improvements in instruments and techniques allow for previously made LASIK flaps to be safely lifted for additional myopic or hyperopic ablations. Newer methods such as Intacs placement provide an effective option for patients who are not good candidates for further ablative procedures. These advancements allow refractive surgeons to treat a wider range of myopia, hyperopia, and astigmatism effectively in eyes with a history of LASIK surgery. PMID:10941651

  11. Influence of an Intensive, Field-Based Life Science Course on Preservice Teachers' Self-Efficacy for Environmental Science Teaching

    Science.gov (United States)

    Trauth-Nare, Amy

    2015-08-01

    Personal and professional experiences influence teachers' perceptions of their ability to implement environmental science curricula and to positively impact students' learning. The purpose of this study was twofold: to determine what influence, if any, an intensive field-based life science course and service learning had on preservice teachers' self-efficacy for teaching about the environment and to determine which aspects of the combined field-based course/service learning preservice teachers perceived as effective for enhancing their self-efficacy. Data were collected from class documents and written teaching reflections of 38 middle-level preservice teachers. Some participants ( n = 18) also completed the Environmental Education Efficacy Belief Instrument at the beginning and end of the semester. Both qualitative and quantitative data analyses indicated a significant increase in PSTs' personal efficacies for environmental teaching, t(17) = 4.50, p = .000, d = 1.30, 95 % CI (.33, .90), but not outcome expectancy, t(17) = 1.15, p = .268, d = .220, 95 % CI (-.06, .20). Preservice teachers reported three aspects of the course as important for enhancing their self-efficacies: learning about ecological concepts through place-based issues, service learning with K-5 students and EE curriculum development. Data from this study extend prior work by indicating that practical experiences with students were not the sole factor in shaping PSTs' self-efficacy; learning ecological concepts and theories in field-based activities grounded in the local landscape also influenced PSTs' self-efficacy.

  12. At-Risk Boys' Social Self-Efficacy and Physical Activity Self-Efficacy in a Summer Sports Camp

    Science.gov (United States)

    Su, Xiaoxia; Xiang, Ping; McBride, Ron E.; Liu, Jiling; Thornton, Michael A.

    2016-01-01

    This study examined at-risk boys' social self-efficacy and physical activity self-efficacy within Bandura's self-efficacy framework. A total of 97 boys, aged between 10 and 13 years, attending a summer sports camp completed questionnaires assessing their social self-efficacy, physical activity self- efficacy, prosocial behaviors, and effort.…

  13. Anti-cancer efficacy of silybin derivatives -- a structure-activity relationship.

    Directory of Open Access Journals (Sweden)

    Chapla Agarwal

    Full Text Available Silybin or silibinin, a flavonolignan isolated from Milk thistle seeds, is one of the popular dietary supplements and has been extensively studied for its antioxidant, hepatoprotective and anti-cancer properties. We have envisioned that potency of silybin could be further enhanced through suitable modification/s in its chemical structure. Accordingly, here, we synthesized and characterized a series of silybin derivatives namely 2,3-dehydrosilybin (DHS, 7-O-methylsilybin (7OM, 7-O-galloylsilybin (7OG, 7,23-disulphatesilybin (DSS, 7-O-palmitoylsilybin (7OP, and 23-O-palmitoylsilybin (23OP; and compared their anti-cancer efficacy using human bladder cancer HTB9, colon cancer HCT116 and prostate carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated better growth inhibitory effects and compared to silybin, while other silybin derivatives showed lesser or no efficacy. Next, we prepared the optical isomers (A and B of silybin, DHS, 7OM and 7OG, and compared their anti-cancer efficacy. Isomers of these three silybin derivatives also showed better efficacy compared with respective silybin isomers, but in each, there was no clear cut silybin A versus B isomer activity preference. Further studies in HTB cells found that DHS, 7OM and 7OG exert better apoptotic activity than silibinin. Clonogenic assays in HTB9 cells further confirmed that both the racemic mixtures as well as pure optical isomers of DHS, 7OM and 7OG were more effective than silybin. Overall, these results clearly suggest that the anti-cancer efficacy of silybin could be significantly enhanced through structural modifications, and identify strong anti-cancer efficacy of silybin derivatives, namely DHS, 7OM, and 7OG, signifying that their efficacy and toxicity should be evaluated in relevant pre-clinical cancer models in rodents.

  14. Evaluating Self-Efficacy Expected of Polytechnic Engineering Students as a Measure of Employability

    Directory of Open Access Journals (Sweden)

    Oguche Innocent Ojonugwa

    2015-07-01

    Full Text Available In the face of increasing unemployment partly due to decreasing employability skills of Nigeria polytechnic students, many graduates of Nigeria polytechnic have a dwindle self-efficacy. 420 HND 2 polytechnic engineering students in north central states of Nigeria were surveyed. Data were collected using questionnaire consisting of 4 Likert-type statements. Student’s self-efficacy was measured by asking students to rate themselves  from 1 (“No confidence” to 4 (“Complete confidence”.The self-efficacy of engineering students in Nigeria polytechnic were examined using mean and standard deviation. The mean score for Self-appraisal, Occupational Information, Goal selection, Planning and Problem solving are as follow (3.32, (2.97, (3.28, (3.082 and (3.012 respectively with self-appraisal scoring higher than the others. These findings enhance our understanding of the importance of self-efficacy in the development of employability skills of polytechnic engineering students in Nigeria, more importantly self-appraisal had the highest mean score. The practical implication is that the teaching style will have to shift from being teacher-centred leaning to student-centred learning in order to address and accommodate the need of student’s self-efficacy.Key words: Self-efficacy; Employability; Employability skills; Nigerian polytechnics; Engineering students

  15. Self-objectification and condom use self-efficacy in women university students.

    Science.gov (United States)

    Parent, Mike C; Moradi, Bonnie

    2015-05-01

    This study investigated the roles of indicators of the self-objectification process in women's condom use self-efficacy. Data were collected from 595 college women. Self-objectification variables were assessed with measures of internalization of cultural standards of beauty, body surveillance, and body shame. Participants also completed measures of perceived control over sexual activity, acceptance of sexuality, and condom use self-efficacy. Measurement and structural invariance were supported, indicating that the measurement model and hypothesized structural model did not differ across participants who were or were not sexually active. Structural equation modeling results were consistent with hypotheses and prior evidence indicating that body surveillance partially mediated the link between internalization of cultural standards of beauty and body shame. Results also indicated that body shame was associated with lower condom use self-efficacy both directly and indirectly through the partial mediation of perceived control over sexual activity; acceptance of sexuality was not a significant mediator of this link but was associated directly with greater condom use self-efficacy. These results connect the substantial literature on the self-objectification process with women's condom use self-efficacy. Specifically, these results point to interrupting the self-objectification process and reducing body shame as well as to enhancing acceptance of sexuality and control over sexual activity as potentially fruitful targets for interventions to promote women's condom use self-efficacy. PMID:25304902

  16. Analysis of cohesion and collective efficacy profiles for the performance of soccer players.

    Science.gov (United States)

    Leo, Francisco M; Sánchez-Miguel, Pedro A; Sánchez-Oliva, David; Amado, Diana; García-Calvo, Tomás

    2013-12-18

    The principal aims of the study were to define different profiles of cohesion and perceived efficacy in soccer players and to measure their differences in performance. The subjects were 235 soccer players in the under-18 category who played in the National League in Spain and 15 coaches whose ages ranged from 29 to 45 years. Diverse instruments to assess cohesion, perceived efficacy, and expectations of success were used in the study. Moreover, we measured playing time and performance. The results of the study proved the existence of four cohesion and efficacy profiles that presented significant differences in expectations of success, playing time, and performance. Furthermore, significant differences were found in the distribution of players in the teams as a function of performance. The main conclusion of this study is that soccer players with higher cohesion and collective efficacy levels belonged to teams that completed the season at the top-level classification. In contrast, athletes with low cohesion and collective efficacy usually played in unsuccessful teams. Coaches and sports psychologists are encouraged to promote both social and task cohesion and collective efficacy to enhance team performance. PMID:24511358

  17. An Analysis on the Effect of Computer Self-Efficacy over Scientific Research Self-Efficacy and Information Literacy Self-Efficacy

    Science.gov (United States)

    Tuncer, Murat

    2013-01-01

    Present research investigates reciprocal relations amidst computer self-efficacy, scientific research and information literacy self-efficacy. Research findings have demonstrated that according to standardized regression coefficients, computer self-efficacy has a positive effect on information literacy self-efficacy. Likewise it has been detected…

  18. Comparison of Nitrogen Fertilizers, Induce and Zinc Addition on Glyphosate Efficacy on Three Different Weed Species.

    OpenAIRE

    Hussein F. Abouziena; Ibraheem M. El-Metwally; H.M. El-Saeid; Megh Singh

    2014-01-01

    Herbicides are often tank-mixed with fertilizers to save time, labour, energy, and equipment costs. However addition of some additives with glyphosate may result in reducing glyphosate efficacy. Therefore we evaluated the potential of three nitrogen sources (ammonium sulphate (AMS) at 2 or 4% w/v, ammonium nitrate (AN) at 1 or 2% w/v, urea at 1 or 2 % w/v), nonionic adjuvant (Induce at 0.05% v/v) and Zn at 250 g Zn/ha (1321 ppm) to enhance glyphosate efficacy on pig weed (Amaranthus retroflex...

  19. Teachers' self-efficacy, motivation adn teaching strategies - Auto-eficacia Docente, Motivación del Profesor y Estrategias de Enseñanza

    Directory of Open Access Journals (Sweden)

    Pedro Rosario

    2009-12-01

    Full Text Available According to previous research, teachers’ efficacy relating to teaching practices is highly dependent on the extent to which they are confident about their own capabilities to manage the new demands on their professional role. The present work aimed at: a gathering information about the way teachers manage different aspects of self-efficacy (i.e., enhancing their instructional process in order to optimize their lessons and engage the students in the learning process, in order to identify homogeneous self-efficacy profiles, b investigating the way these profiles relate to different levels and types of motivation, teaching strategies and teachers’ self-esteem. Ninety-five teachers from five Spanish public Universities participated in this study. Three different profiles of teachers’ efficacy have been identified: 1 high self-efficacy in the three dimensions; 2 medium self-efficacy in the enhancement of the teaching process and of lessons management, and medium-high efficacy in the engagement of students, and 3 low self-efficacy in the three dimensions. ANOVA results supported previous findings since teachers’ self-efficacy beliefs played a crucial role on teachers’ motivation and professional engagement.

  20. Breastfeeding self-efficacy among adolescent mothers

    Directory of Open Access Journals (Sweden)

    Renata de Lima Bizerra

    2015-09-01

    Full Text Available The objective of the study was to assess breastfeeding self-efficacy among lactating adolescents. A quantitative study involving 172 lactating adolescents, conducted in 14 Basic Health Units in the northeast cities of Brazil. For data collection, we used a form and the Breastfeeding Self-Efficacy Scale – Short Form. Data were analyzed with a statistical software. Results showed high breastfeeding self-efficacy (84%, with more adherence to the items: “Ensure that my baby is properly latched on for the whole feeding” (91%, and “Always recognize then my baby is finished breastfeeding” (93%, and less referent to feed the baby without using formula (18% and breastfeed in front of people (14%. We found high breastfeeding self-efficacy in adolescent mothers in our study, showing a new knowledge about this specific public, in general, related to breastfeeding vulnerability.

  1. Developing the Reader Self-Efficacy Scale

    OpenAIRE

    ÜLPER, Hakan; Derya YAYLI; İsmail KARAKAYA

    2013-01-01

    Reading comprehension has affective and social dimensions as well as its cognitive dimension. Thus, to understand and improve reading instruction, affective and social dimensions should be well understood. Perceived self-efficacy is one of affective issues influencing learning and it should be taken into consideration in reading instruction. With this in mind, this study aims at developing the Reader Self-Efficacy Scale with a group of 518 students as participants. Exploratory and confirmator...

  2. Safety and Efficacy of Modern Insulin Analogues

    OpenAIRE

    Hye Jin Yoo; Keun Yong Park; Kang Seo Park; Kyu Jeung Ahn; Kyung Wan Min; Jeong Hyun Park; Sang Ah Chang; Bong Soo Cha; Dong-Jun Kim; Yong Seong Kim; Tae Keun Oh; Suk Chon; Il Seong Nam-Goong; Mi Jin Kim; Hye-Soon Kim

    2013-01-01

    Background A1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. Methods Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at base...

  3. Percieved Organizational Efficacy in Internationalized Companies: Application of Competing Values Approach and Collective Efficacy

    OpenAIRE

    Kravchenko, Evgeniya

    2014-01-01

    This dissertation focuses on “organizational efficacy”, in particular on employees’ beliefs of organizational capacity to be efficacious. Organizational efficacy is considered from two perspectives – competing values approach and collective efficacy, and evaluated in internationalized companies. The dissertation is composed of three studies. The data were collected in thirteen Italian companies on different stages of internationalization for a total number of respondents is 358. In the first ...

  4. Comparative efficacy of alcohol-based surgical scrubs: the importance of formulation.

    Science.gov (United States)

    Macinga, David R; Edmonds, Sarah L; Campbell, Esther; McCormack, Robert R

    2014-12-01

    Alcohol-based surgical scrubs (ABSSs) are used to prevent surgical site infections. Chlorhexidine gluconate (CHG) often is added to enhance persistent germicidal activity. The aim of this study was to determine the influence of ABSS product formulation on efficacy. We evaluated three commercially available ABSS formulations and one control alcohol formulation according to the surgical scrub methodology specified by the US Food and Drug Administration (FDA). Only one ABSS formulation met FDA efficacy requirements when tested at the manufacturer's recommended dosage. In contrast, two ABSS formulations, one of which contained CHG, failed to meet the FDA acceptance criteria for a 3-log10 reduction on day 5, meaning the formulations did not sufficiently reduce bacteria levels on hands on the fifth day of product application. The data suggest that recommendations to include CHG in ABSS formulations should be reconsidered, and product efficacy, skin tolerability, and user acceptability should be evaluated on a case-by-case basis. PMID:25453683

  5. Examining teacher self-efficacy about best practices in science during a professional development series

    Science.gov (United States)

    Menez, Jessica L.

    Using extant data that were collected as part of a larger project, the current study examined teacher self-efficacy and the teachers' intentions to implement workshop content throughout the course of a six-week professional development workshop focused on enhancing science motivation for students through the adoption of specific instructional strategies. There were a total of 20 middle and high school teacher participants. Results indicated teacher self-efficacy changed significantly from pre to post. Teachers showed higher teacher self-efficacy after the professional development, in particular for influencing student engagement. In addition, we found a moderate correlation between the level of confidence after the implementation of a strategy and teachers intention of trying the strategy again. Finally, new direction for future research topics made possible by this study are presented.

  6. Instrumented and interactive limb models for biomechanics education: An assessment of efficacy and engagement.

    Science.gov (United States)

    Sulas, Romina; Liem, Nicholas; Kark, Lauren

    2015-08-01

    Custom anatomical and instrumented models of the human arm and leg were designed and manufactured to complement the teaching of introductory biomechanics subjects. The models were assessed for engagement and efficacy via questionnaires and unscheduled pop-quizzes, respectively. Questionnaire results demonstrated the ability of the models to provide assistance with understanding and visualising the fundamental principles of biomechanics. Additionally, the majority of students who participated also stated that the models enhanced their motivation to learn and stimulated their interest in biomechanics. Results from the pop-quizzes were ambiguous about the efficacy of the arm and leg models; only one group (out of five) showed significant improvements in pop-quiz scores following exposure to the models. Significance was not reached in the remaining groups. Further assessment is required to expose the true efficacy of the models. PMID:26737089

  7. Speech Enhancement

    DEFF Research Database (Denmark)

    Benesty, Jacob; Jensen, Jesper Rindom; Christensen, Mads Græsbøll;

    and their performance bounded and assessed in terms of noise reduction and speech distortion. The book shows how various filter designs can be obtained in this framework, including the maximum SNR, Wiener, LCMV, and MVDR filters, and how these can be applied in various contexts, like in single......Speech enhancement is a classical problem in signal processing, yet still largely unsolved. Two of the conventional approaches for solving this problem are linear filtering, like the classical Wiener filter, and subspace methods. These approaches have traditionally been treated as different classes...

  8. The Influence of Delivery Vectors on HIV Vaccine Efficacy

    Directory of Open Access Journals (Sweden)

    BeatriceOmusiroOndondo

    2014-08-01

    Full Text Available Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximise transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502 where human adenovirus serotype 5 (Ad5 was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared towards delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy.

  9. The influence of delivery vectors on HIV vaccine efficacy.

    Science.gov (United States)

    Ondondo, Beatrice O

    2014-01-01

    Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy. PMID:25202303

  10. Multifaceted Impact of Self-Efficacy Beliefs on Academic Functioning.

    Science.gov (United States)

    Bandura, Albert; And Others

    1996-01-01

    Analyzed the psychosocial influences through which efficacy beliefs affect academic achievement. Found that parents' sense of academic efficacy and aspirations for their children, children's beliefs in their efficacy to regulate their own learning and academic attainments, children's perceived social efficacy and ability to manage peer pressure,…

  11. Development of a Physical Education Teaching Efficacy Scale

    Science.gov (United States)

    Humphries, Charlotte A.; Hebert, Edward; Daigle, Kay; Martin, Jeffrey

    2012-01-01

    Relationships have been found between teacher efficacy and many teaching and learning variables, but few researchers have examined teaching efficacy in physical education. The instrument reported here, the Physical Education Teaching Efficacy Scale, was developed based on the teaching efficacy literature, existing scales, and National Association…

  12. EDITORIAL: Enhancing nanolithography Enhancing nanolithography

    Science.gov (United States)

    Demming, Anna

    2012-01-01

    Lithography was invented in late 18th century Bavaria by an ambitious young playwright named Alois Senefelder. Senefelder experimented with stone, wax, water and ink in the hope of finding a way of reproducing text so that he might financially gain from a wider distribution of his already successful scripts. His discovery not only facilitated the profitability of his plays, but also provided the world with an affordable printing press that would ultimately democratize the dissemination of art, knowledge and literature. Since Senefelder, experiments in lithography have continued with a range of innovations including the use of electron beams and UV that allow increasingly higher-resolution features [1, 2]. Applications for this have now breached the limits of paper printing into the realms of semiconductor and microelectronic mechanical systems technology. In this issue, researchers demonstrate a technique for fabricating periodic features in poly(3,4-ethylene dioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) [3]. Their method combines field enhancements from silica nanospheres with laser-interference lithography to provide a means of patterning a polymer that has the potential to open the market of low-end, high-volume microelectronics. Laser-interference lithography has already been used successfully in patterning. Researchers in Korea used laser-interference lithography to generate stamps for imprinting a two-dimensional photonic crystal structure into green light emitting diodes (LEDs) [4]. The imprinted patterns comprised depressions 100 nm deep and 180 nm wide with a periodicity of 295 nm. In comparison with unpatterned LEDs, the intensity of photoluminescence was enhanced by a factor of seven in the LEDs that had the photonic crystal structures imprinted in them. The potential of exploiting field enhancements around nanostructures for new technologies has also attracted a great deal of attention. Researchers in the USA and Australia have used the field

  13. Antigen specificity can be irrelevant to immunocytokine efficacy and biodistribution.

    Science.gov (United States)

    Tzeng, Alice; Kwan, Byron H; Opel, Cary F; Navaratna, Tejas; Wittrup, K Dane

    2015-03-17

    Cytokine therapy can activate potent, sustained antitumor responses, but collateral toxicity often limits dosages. Although antibody-cytokine fusions (immunocytokines) have been designed with the intent to localize cytokine activity, systemic dose-limiting side effects are not fully ameliorated by attempted tumor targeting. Using the s.c. B16F10 melanoma model, we found that a nontoxic dose of IL-2 immunocytokine synergized with tumor-specific antibody to significantly enhance therapeutic outcomes compared with immunocytokine monotherapy, concomitant with increased tumor saturation and intratumoral cytokine responses. Examination of cell subset biodistribution showed that the immunocytokine associated mainly with IL-2R-expressing innate immune cells, with more bound immunocytokine present in systemic organs than the tumor microenvironment. More surprisingly, immunocytokine antigen specificity and Fcγ receptor interactions did not seem necessary for therapeutic efficacy or biodistribution patterns because immunocytokines with irrelevant specificity and/or inactive mutant Fc domains behaved similarly to tumor-specific immunocytokine. IL-2-IL-2R interactions, rather than antibody-antigen targeting, dictated immunocytokine localization; however, the lack of tumor targeting did not preclude successful antibody combination therapy. Mathematical modeling revealed immunocytokine size as another driver of antigen targeting efficiency. This work presents a safe, straightforward strategy for augmenting immunocytokine efficacy by supplementary antibody dosing and explores underappreciated factors that can subvert efforts to purposefully alter cytokine biodistribution. PMID:25733854

  14. Double-Blind, Randomized Study of the Efficacy and Safety of Oral Pharmacokinetically Enhanced Amoxicillin-Clavulanate (2,000/125 Milligrams) versus Those of Amoxicillin-Clavulanate (875/125 Milligrams), Both Given Twice Daily for 7 Days, in Treatment of Bacterial Community-Acquired Pneumonia in Adults

    OpenAIRE

    File, T M; Lode, H; Kurz, H.; Kozak, R; H. Xie; Berkowitz, E

    2004-01-01

    This randomized, double-blind, noninferiority trial was designed to demonstrate that pharmacokinetically enhanced amoxicillin-clavulanate (2,000/125 mg) was at least as effective clinically as amoxicillin-clavulanate 875/125 mg, both given twice daily for 7 days, in the treatment of community-acquired pneumonia in adults. In total, 633 clinically and radiologically confirmed community-acquired pneumonia patients (intent-to-treat population) were randomized to receive either oral amoxicillin-c...

  15. Coping self-efficacy mediates the effects of negative cognitions on posttraumatic distress.

    Science.gov (United States)

    Cieslak, Roman; Benight, Charles C; Caden Lehman, Victoria

    2008-07-01

    Although cognitive distortions have predicted posttraumatic distress after various types of traumatic events, the mechanisms through which cognitive distortions influence posttraumatic distress remain unclear. We hypothesized that coping self-efficacy, the belief in one's own ability to manage posttraumatic recovery demands, would operate as a mediator between negative cognitions (about self, about the world, and self-blame beliefs) and posttraumatic distress. In the cross-sectional Study 1, data collected among 66 adult female victims of child sexual abuse indicated that coping self-efficacy mediated the effects of negative cognitions about self and about the world on posttraumatic distress. The same pattern of results was found in a longitudinal Study 2, conducted among 70 survivors of motor vehicle accidents. Coping self-efficacy measured at 1 month after the trauma mediated the effects of 7-day negative cognitions about self and about the world on 3-month posttraumatic distress. In both studies self-blame was not related to posttraumatic distress and the effect of self-blame on posttraumatic distress was not mediated by coping self-efficacy. The results provide insight into a mechanism through which negative cognitions may affect posttraumatic distress and highlight the potential importance of interventions aimed at enhancing coping self-efficacy beliefs. PMID:18456241

  16. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice

    Institute of Scientific and Technical Information of China (English)

    Zheng-hong WU; Qi-neng PING; Yi WEI; Jia-ming LAI

    2004-01-01

    AIM: To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitoring the blood glucose level using the glucose oxidase method after oral administration to healthy mice. RESULTS:In all the insulin liposomes, the insulin liposomes coated by 0.2 % chitosan (M. 1000 kDa) showed a better hypoglycemic efficacy as compared with the other liposomes coated by chitosan. The minimum blood glucose level was 15.1%±6.0 % of the initial (n=6). The hypoglycemic efficacy lasted for 4 h after oral administration to mice.CONCLUSION: Chitosan-coated liposomes could reduce tryptic digestion on insulin, and enhance enteral absorption of insulin. The molecular weights and concentrations of chitosan had significant effects on hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration to healthy mice.

  17. Association of Self-Efficacy and Outcome Expectations with Physical Activity in Adults with Arthritis

    Directory of Open Access Journals (Sweden)

    Thelma J. Mielenz

    2013-01-01

    Full Text Available Background and Purpose. The purpose of this study is to determine whether higher baseline levels of (a self-efficacy for physical activity, (b self-efficacy for arthritis self-management, and (c outcome expectations for exercise are associated with higher physical activity levels following an exercise intervention for adults with arthritis. Methods. A secondary analysis of the intervention cohort (n=130 within a randomized controlled trial of the People with Arthritis Can Exercise program was performed. Multiple linear regression evaluated the relationship between physical activity at a time point three months after the completion of an exercise intervention and three main explanatory variables. Results. After controlling for baseline physical activity, neither self-efficacy for arthritis self-management nor outcome expectations for exercise related to three-month physical activity levels. There was a relationship between three-month physical activity and self-efficacy for physical activity. Conclusions. Future research is needed to evaluate the ability of self-efficacy-enhancing programs to increase physical activity in adults with arthritis.

  18. Co-constructing Efficacy: A "Communities of Practice" Perspective on Teachers' Efficacy Beliefs

    Science.gov (United States)

    Takahashi, Sola

    2011-01-01

    Teachers' efficacy beliefs are critical to improving student learning, but we have yet to fully understand how these beliefs develop. The prevailing model of teachers' efficacy development emerges from cognitive theories, but sociocultural theories may add insights to modeling the impact of teachers' school contexts. This case study takes a…

  19. Does Emotional Self-Efficacy Predict Teachers' Self-Efficacy and Empathy?

    Science.gov (United States)

    Goroshit, Mariana; Hen, Meirav

    2014-01-01

    Research has shown that teachers' self-efficacy and empathy are two of the most important variables consistently related to outcomes of positive teaching and student learning. Emotional self-efficacy refers to peoples' judgment regarding their own capacity to process emotional information accurately and effectively. It is considered a powerful…

  20. A Climate for Self-Efficacy: The Relationship between School Climate and Teacher Efficacy for Inclusion

    Science.gov (United States)

    Hosford, Susan; O'Sullivan, Siobhán

    2016-01-01

    Teacher efficacy represents a key construct in exploring successful implementation of inclusive policy. Teachers' impression of school climate is shown to relate to teacher efficacy; however, few studies pay due deference to its context/specific conceptualisation, with a particular lacuna in research noted in an Irish mainstream primary school…

  1. Self-efficacy and outcome expectancy in beginning weight training class: their relations to students' behavioral intention and actual behavior.

    Science.gov (United States)

    Gao, Zan; Xiang, Ping; Lee, Amelia M; Harrison, Louis

    2008-03-01

    This study was an initial attempt to investigate the relationships among self-efficacy, outcome expectancy, behavioral intention, and actual behavior over time in a beginning weight training class. A total of 109 participants completed questionnaires assessing their self-efficacy, outcome expectancy, and intentions for future weight training. Their attendance and workout logs were calculated as a measure of actual behavior. Correlation analyses revealed significant positive relationships among all the variables during both program periods. Multiple regression analyses indicated that outcome expectancy initially played a more important role than self-efficacy in predicting behavioral intention and actual behavior. However, self-efficacy appeared more influential at midprogram. Findings of this study can enhance our understanding of the determining factors for individuals' motivated behaviors in college physical activity classes. PMID:18431955

  2. Developing the Reader Self-Efficacy Scale

    Directory of Open Access Journals (Sweden)

    Hakan ÜLPER

    2013-04-01

    Full Text Available Reading comprehension has affective and social dimensions as well as its cognitive dimension. Thus, to understand and improve reading instruction, affective and social dimensions should be well understood. Perceived self-efficacy is one of affective issues influencing learning and it should be taken into consideration in reading instruction. With this in mind, this study aims at developing the Reader Self-Efficacy Scale with a group of 518 students as participants. Exploratory and confirmatory factor analyses revealed a 6-item scale with one factor. The Cronbach Alpha coefficient was determined to be 0.948. This new Reader Self-Efficacy Scale could easily be used for training and research purposes depending on its high validity and reliability.

  3. An investigation of the influence of gender and menstrual cycle phase on metacognitive judgments of efficacy

    OpenAIRE

    Whitfield, Kevin

    2005-01-01

    Verbal memory, verbal working memory, processing speed and visual attention have been reported to be enhanced in the luteal phase of the menstrual cycle, as compared with the menstrual phase. However, many women report diminished cognitive abilities in the luteal phase, as compared with other phases of the menstrual cycle. This study attempted to examine the nature of the apparent discrepancy between cognitive functioning and self reported cognitive efficacy. Participants completed a battery ...

  4. Interprofessional clinical training improves self-efficacy of health care students

    DEFF Research Database (Denmark)

    Nørgaard, Birgitte; Draborg, Eva; Vestergaard, Erik;

    2013-01-01

    ) and a comparison group (405 students). The intervention was provided by an interprofessional clinical study unit (ICS) and included students from nursing, medicine, physiotherapy, occupational therapy, laboratory technology and radiography. Self-efficacy data were collected through web-based questionnaires......Background: Interprofessional collaboration potentially enhances patient safety and satisfaction, and reduces tensions and conflicts among health care professionals. Such collaboration is challenging, however, because health care professionals lack sufficient knowledge of other professional roles...

  5. Efficacy of Adolescent Suicide Prevention E-Learning Modules for Gatekeepers: A Randomized Controlled Trial

    OpenAIRE

    Ghoncheh, Rezvan; Gould, Madelyn S.; Twisk, Jos WR; Kerkhof, Ad JFM; Koot, Hans M

    2016-01-01

    Background Face-to-face gatekeeper training can be an effective strategy in the enhancement of gatekeepers’ knowledge and self-efficacy in adolescent suicide prevention. However, barriers related to access (eg, time, resources) may hamper participation in face-to-face training sessions. The transition to a Web-based setting could address obstacles associated with face-to-face gatekeeper training. Although Web-based suicide prevention training targeting adolescents exists, so far no randomized...

  6. The Carpentier-Edwards Perimount Magna mitral valve bioprosthesis: intermediate-term efficacy and durability

    OpenAIRE

    Loor, Gabriel; Schuster, Andres; Cruz, Vincent; Rafael, Aldo; Stewart, William J.; Diaz, James; McCurry, Kenneth

    2016-01-01

    Background The Carpentier-Edwards Perimount Magna mitral valve bioprosthesis (Edwards Lifesciences, Irvine, CA) is a low-profile version of the earlier Perimount valve that uses the ThermaFix process for enhanced calcium removal. The Magna valve has been in use since 2008, yet no publication, until now, has verified its intermediate-term safety and efficacy. Methods From 2008 through 2011 (our 4-year study period), 70 Magna valves were implanted in the mitral position at a single institution ...

  7. Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation among nursing home residents

    OpenAIRE

    Kim Jung; Kim Mi; Lee Do; Jang Seok; Baek Eun; An Hyang; Lee Kang; Park Jong; Ha Nam

    2010-01-01

    Abstract Background Constipation is a significant problem in the elderly, specifically nursing home and/or extended-care facility residents are reported to suffer from constipation. Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as diarrhea and constipation effect. The objective of this study was to investigate the efficacy of this LAB supplement in the management o...

  8. Transformational Leaders and Work Performance: The Mediating Roles of Identification and Self-efficacy

    OpenAIRE

    Flávia Cavazotte; Valter Moreno; Jane Bernardo

    2013-01-01

    In this study we investigate the connections between transformational leadership and subordinate formal and contextual performance among Brazilian employees. We also proposed and tested two mediating processesthrough which transformational leaders would enhance the performance of their staff: stronger follower identification with the leader and efficacy beliefs. These relations were tested with a sample of 107 managers from a multinational company that operates in the financial sector. The pr...

  9. Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction

    OpenAIRE

    Das, Anindita; Durrant, David; Mitchell, Clint; Mayton, Eric; Hoke, Nicholas N.; Salloum, Fadi N.; Park, Margaret A.; Qureshi, Ian; Lee, Ray; Dent, Paul; Kukreja, Rakesh C.

    2010-01-01

    We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra) induces a powerful effect on reduction of infarct size following ischemia/reperfusion injury and improvement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin (DOX) treatment. In the present study, we further investigated the potential effects of sildenafil on improving antitumor efficacy of DOX in prostate cancer. Cotreatment with sildenafil enhanced DOX-induc...

  10. Self-efficacy in English : a comparison of first year and fourth year students' language self-efficacy in the Philippines and the factors affecting self-efficacy

    OpenAIRE

    2010-01-01

    Self-efficacy beliefs are “beliefs in one‟s capability to organize and perform courses of action needed to handle prospective situations” (Bandura, 1997). Academically, students with a high sense of efficacy for accomplishing a task will get involved more readily, work harder, and persist longer than those who doubt their capabilities (Zimmerman, 1995). As self-efficacy is known to influence student achievement, the study aimed to investigate the English self-efficacy of Filipino students ...

  11. Efficacy and Safety of Pharmacokinetically Enhanced Amoxicillin-Clavulanate at 2,000/125 Milligrams Twice Daily for 5 Days versus Amoxicillin-Clavulanate at 875/125 Milligrams Twice Daily for 7 Days in the Treatment of Acute Exacerbations of Chronic Bronchitis

    OpenAIRE

    Sethi, Sanjay; Breton, John; Wynne, Brian

    2005-01-01

    This randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment of acute exacerbations of chronic bronchitis (AECB). Amoxicillin-clavulanate at 2,000/125 mg was designed to extend the therapeutic levels of amoxicillin in serum over the 12-h do...

  12. Self-Efficacy and green entrepreneurship

    Science.gov (United States)

    Tan, K. L.; Suhaida, S.; Leong, Y. P.

    2013-06-01

    The objective of this study is to investigate empirically the extent to which self-efficacy contributes to the development of green entrepreneurial intention. The measurement constructs of self-efficacy were classified into market opportunities, innovative environment, initiating relationships, defining purpose, coping with challenges, and developing human resources. The study comprises 252 usable convenient samples through structured questionnaires. The coefficient of determination R2 shows that the variance of intention to entrepreneurship is explained by the variance of the independent variables. It was also found that the model is fit for prediction.

  13. Self-efficacy expectations among traumatized adolescents.

    Science.gov (United States)

    Saigh, P A; Mroueh, M; Zimmerman, B J; Fairbank, J A

    1995-07-01

    Bandura's Multidimensional Scales of Perceived Self-Efficacy (MSPSE) were administered to three matched groups of adolescents. The first group met diagnostic criteria for PTSD. The second had been exposed to qualitatively and quantitatively similar stressors and did not meet criteria for PTSD (traumatized PTSD negatives). The third group consisted of non-traumatized controls. Data analysis revealed that the adolescents with PTSD had appreciably lower self-efficacy ratings on eight of the nine subtests that comprise the MSPSE. Non-significant differences were observed when the MSPSE subtest scores of the traumatized PTSD negatives and controls were compared. PMID:7654163

  14. Self-Efficacy and green entrepreneurship

    International Nuclear Information System (INIS)

    The objective of this study is to investigate empirically the extent to which self-efficacy contributes to the development of green entrepreneurial intention. The measurement constructs of self-efficacy were classified into market opportunities, innovative environment, initiating relationships, defining purpose, coping with challenges, and developing human resources. The study comprises 252 usable convenient samples through structured questionnaires. The coefficient of determination R2 shows that the variance of intention to entrepreneurship is explained by the variance of the independent variables. It was also found that the model is fit for prediction.

  15. The Efficacy of Positive Psychology Interventions to Increase Well-Being and the Role of Mental Imagery Ability

    Science.gov (United States)

    Odou, Natasha; Vella-Brodrick, Dianne A.

    2013-01-01

    This study examined the effects of mental imagery ability (MIA) on the efficacy of two positive psychology interventions (PPIs) to enhance well-being. Participants (N = 210) were randomly assigned to either: Three Good Things (TGT), Best Possible Selves (BPS), or a control group and completed well-being questionnaires pre and post intervention.…

  16. The Trainee in Context: Examining the Relationship between Self-Efficacy and Transfer Climate for Transfer of Training

    Science.gov (United States)

    Sookhai, Fiona; Budworth, Marie-Helene

    2010-01-01

    Trainee perceptions of transfer climate have been found to be an important predictor of transfer of training. Self-efficacy has also been identified as an important individual difference related to transfer. Few studies have examined how these variables work together to enhance or limit performance following training. In a field study of 37…

  17. Effects of a Metacognitive Intervention on Students' Approaches to Learning and Self-Efficacy in a First Year Medical Course

    Science.gov (United States)

    Papinczak, Tracey; Young, Louise; Groves, Michele; Haynes, Michele

    2008-01-01

    Aim: To determine the influence of metacognitive activities within the PBL tutorial environment on the development of deep learning approach, reduction in surface approach, and enhancement of individual learning self-efficacy. Method: Participants were first-year medical students (N = 213). A pre-test, post-test design was implemented with…

  18. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy.

    Science.gov (United States)

    Lee, Dylan E; Ayoub, Nagi; Agrawal, Devendra K

    2016-01-01

    Mesenchymal stem cells (MSCs) (also known as multipotent mesenchymal stromal cells) possess the capacity for self-renewal and multi-lineage differentiation, and their ability to enhance cutaneous wound healing has been well characterized. Acting via paracrine interactions, MSCs accelerate wound closure, increase angiogenesis, promote resolution of wound inflammation, favorably regulate extracellular matrix remodeling, and encourage regeneration of skin with normal architecture and function. A number of studies have employed novel methods to amplify the delivery and efficacy of MSCs. Non-traditional sources of MSCs, including Wharton's jelly and medical waste material, have shown efficacy comparable to that of traditional sources, such as bone marrow and adipose tissue. The potential of alternative methods to both introduce MSCs into wounds and increase migration of MSCs into wound areas has also been demonstrated. Taking advantage of the associations between MSCs with M2 macrophages and microRNA, methods to enhance the immunomodulatory capacity of MSCs have shown success. New measures to enhance angiogenic capabilities have also exhibited effectiveness, often demonstrated by increased levels of proangiogenic vascular endothelial growth factor. Finally, hypoxia has been shown to have strong wound-healing potential in terms of increasing MSC efficacy. We have critically reviewed the results of the novel studies that show promise for the continued development of MSC-based wound-healing therapies and provide direction for continued research in this field. PMID:26960535

  19. Sweat Therapy Theory, Practice, and Efficacy

    Science.gov (United States)

    Eason, Allen; Colmant, Stephen; Winterowd, Carrie

    2009-01-01

    The purpose of this article is to examine the potential application of sweat rituals to group counseling, adventure therapy, and other forms of group work by describing a theoretical model for how sweat rituals work and presenting the results of a randomized comparative outcome study on the efficacy of sweat therapy. The theoretical model proposes…

  20. Evaluating Ritual Efficacy: Evidence from the Supernatural

    Science.gov (United States)

    Legare, Cristine H.; Souza, Andre L.

    2012-01-01

    Rituals pose a cognitive paradox: although widely used to treat problems, rituals are causally opaque (i.e., they lack a causal explanation for their effects). How is the efficacy of ritual action evaluated in the absence of causal information? To examine this question using ecologically valid content, three studies (N=162) were conducted in…

  1. Promoting Efficacy Research on Functional Analytic Psychotherapy

    Science.gov (United States)

    Maitland, Daniel W. M.; Gaynor, Scott T.

    2012-01-01

    Functional Analytic Psychotherapy (FAP) is a form of therapy grounded in behavioral principles that utilizes therapist reactions to shape target behavior. Despite a growing literature base, there is a paucity of research to establish the efficacy of FAP. As a general approach to psychotherapy, and how the therapeutic relationship produces change,…

  2. Leadership, Self-Efficacy, and Student Achievement

    Science.gov (United States)

    Grayson, Kristin

    2013-01-01

    This study examined the relationships between teacher leadership, science teacher self-efficacy, and fifth-grade science student achievement in diverse schools in a San Antonio, Texas, metropolitan school district. Teachers completed a modified version of the "Leadership Behavior Description Question" (LBDQ) Form XII by Stogdill (1969),…

  3. Self-Efficacy and Academic Listening

    Science.gov (United States)

    Graham, Suzanne

    2011-01-01

    This paper takes as its starting point the difficulties inherent in listening in a second language. It argues that self-efficacy, broadly defined as the belief in one's ability to carry out specific tasks successfully, is crucial to the development of effective listening skills, and that listening strategy instruction has the potential to boost…

  4. Self-Efficacy and Music Performance

    Science.gov (United States)

    McPherson, Gary E.; McCormick, John

    2006-01-01

    This study is the second in a series of investigations attempting to clarify relationships between variables that impact on a young musician's ability to perform music (as assessed on a graded music examination). Consistent with studies on school academic subjects, our previous investigation demonstrated the importance of self-efficacy in…

  5. Safety and efficacy of two manual toothbrushes.

    NARCIS (Netherlands)

    Rosema, N.A.; Timmerman, M.F.; Versteeg, P.A.; Palenstein Helderman, W.H. van; Velden, U. van den; Weijden, G.A. van der

    2010-01-01

    OBJECTIVE: The purpose of this study was to test the efficacy and safety of a newly designed multi-level manual toothbrush (Profit-Haije-Brush) compared with a control flat-trimmed manual reference toothbrush from the American Dental Association (ADA). MATERIAL AND METHODS: For this study, 36 health

  6. Clinical Efficacy of ciprofloxacin and ofloxacin

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    The cliniueal efficacy, antibacterial activity and adverse effects of ciprofloxacin (CPLX) and ofloxacin (OFLX) produced in our country were compared in five clinical hospitals in Beijing and Guangzhou in 1992. Two groups, each consisting of 100 cases, were treated with. CPLX and OFLX respectively. The total

  7. Arsenic trioxide enhances the therapeutic efficacy of adjuvant post-operative chemotherapy of gastric carcinoma while protecting bone marrow%三氧化二砷改善胃癌患者术后辅助化疗疗效同时减轻骨髓抑制

    Institute of Scientific and Technical Information of China (English)

    Hong Sui; Yuxian Bai; Yu Han; Kaibing Wang

    2009-01-01

    Objective: The aim of the study was to investigate the prospective study if treatment with arsenic trioxide (As2O3) could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods: 84 adults were randomized into two groups. Patients in treat- ment group were treated with As203 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results: Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety (n = 2), ar- rhythmia (n = 1) and AST/ALT elevation (n = 1), while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months (95% CI, 25-33 months). While in control group, the median DFS was 24.50 months (95% CI, 20-30 months). This difference was not statistically significant (chi-square: 2.8885; P value: 0.0892). Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months (95% CI, 25-31 months) in the treatment group and 24.18 months (95% CI, 19-31 months) in the control group with promising statistical significance (HR 1.89; chi-square: 4.78; P value: 0.0287). The most common grades 3-4 toxicity was leucopenia (n = 11) in control group and the difference was significant (chi-square: 3.9768, P value: 0.046) compared with that in treatment group (n = 4). Conclusion: The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-opera- tive chemotherapy, and protect bone marrow from the negative effects of chemotherapy.

  8. Contrast enhanced ultrasound of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kazushi Numata, Wen Luo, Manabu Morimoto, Masaaki Kondo, Yosuke Kunishi, Tomohiko Sasaki, Akito Nozaki, Katsuaki Tanaka

    2010-02-01

    Full Text Available Sonazoid (Daiichi Sankyo, Tokyo, Japan, a second-generation of a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent, has been used clinically in patients with liver tumors and for harmonic gray-scale ultrasonography (US in Japan since January 2007. Sonazoid-enhanced US has two phases of contrast enhancement: vascular and late. In the late phase of Sonazoid-enhanced US, we scanned the whole liver using this modality at a low mechanical index (MI without destroying the microbubbles, and this method allows detection of small viable hepatocellular carcinoma (HCC lesions which cannot be detected by conventional US as perfusion defects in the late phase. Re-injection of Sonazoid into an HCC lesion which previously showed a perfusion defect in the late phase is useful for confirming blood flow into the defects. High MI intermittent imaging at 2 frames per second in the late phase is also helpful in differentiation between necrosis and viable hypervascular HCC lesions. Sonazoid-enhanced US by the coded harmonic angio mode at a high MI not only allows clear observation of tumor vessels and tumor enhancement, but also permits automatic scanning with Sonazoid-enhanced three dimensional (3D US. Fusion images combining US with contrast-enhanced CT or contrast-enhanced MRI have made it easy to detect typical or atypical HCC lesions. By these methods, Sonazoid-enhanced US can characterize liver tumors, grade HCC lesions histologically, recognize HCC dedifferentiation, evaluate the efficacy of ablation therapy or transcatheter arterial embolization, and guide ablation therapy for unresectable HCC. This article reviews the current developments and applications of Sonazoid-enhanced US and Sonazoid-enhanced 3D US for diagnosing and treating hepatic lesions, especially HCC.

  9. MOTOR IMAGERY AND TENNIS SERVE PERFORMANCE: THE EXTERNAL FOCUS EFFICACY

    Directory of Open Access Journals (Sweden)

    Aymeric Guillot

    2013-06-01

    Full Text Available There is now ample evidence that motor imagery (MI contributes to enhance motor performance. Previous research also demonstrated that directing athletes' attention to the effects of their movements on the environment is more effective than focusing on the action per se. The present study aimed therefore at evaluating whether adopting an external focus during MI contributes to enhance tennis serve performance. Twelve high-level young tennis players were included in a test-retest procedure. The effects of regular training were first evaluated. Then, players were subjected to a MI intervention during which they mentally focused on ball trajectory and specifically visualized the space above the net where the serve can be successfully hit. Serve performance was evaluated during both a validated serve test and a real match. The main results showed a significant increase in accuracy and velocity during the ecological serve test after MI practice, as well as a significant improvement in successful first serves and won points during the match. Present data therefore confirmed the efficacy of MI in combination of physical practice to improve tennis serve performance, and further provided evidence that it is feasible to adopt external attentional focus during MI. Practical applications are discussed

  10. Linalool Affects the Antimicrobial Efficacy of Essential Oils.

    Science.gov (United States)

    Herman, Anna; Tambor, Krzysztof; Herman, Andrzej

    2016-02-01

    The high concentrations of essential oils are generally required to receive microbial purity of the products (cosmetics, medicine). On the other hand, their application due to the high concentration of essential oils may be limited by changes in organoleptic and textural quality of the products, as well as they cause irritation and allergies in users. Addition of linalool to essential oil may significantly enhance its antimicrobial effectiveness and reduce their concentrations in products, taking advantage of their synergistic and additive effects. The aim of the study was to compare antimicrobial activity of essential oil alone and in combination with linalool. The antimicrobial activity of the essential oil of Thymus vulgaris, Juniperus communis, Pelargonium graveolens, Citrus bergamia, Citrus grandis, Lavandula angustifolia, Cinnamomum zeylanicum, Melaleuca alternifolia, Syzygium aromaticum, linalool and their combination was investigated against bacteria and fungi using the disc diffusion method. The addition of linalool to S. aromaticum oil in a synergistic manner enhanced its antimicrobial efficacy against P. aeruginosa and A. brasiliensis. Moreover, the additive interaction between this oil and linalool was observed against S. aureus, E. coli and C. albicans. It was also found that linalool in an additive manner increased the antimicrobial effectiveness of T. vulgaris oil against P. aeruginosa. The antimicrobial properties of mixture of essential oils with their active constituents may be used for creating new strategies to maintain microbiological purity of products. PMID:26553262

  11. The role of self-efficacy, emotional intelligence and leadership style as attributes of leadership effectiveness

    Directory of Open Access Journals (Sweden)

    Yvette Ramchunder

    2014-02-01

    Full Text Available Orientation: Researching the impact of psychological constructs on police leadership may add value when appointing people in leadership positions or developing people for leadership roles in the police environment.Research purpose: The purpose of this study is to explore the relationship between three constructs, namely emotional intelligence, self-efficacy and leadership effectiveness in a policing context.Motivation for this study: In the police sector, there are difficulties in linking leadership to organisational outcomes since common police-leadership measures are affected by multiple contributory factors. This study explores the psychological constructs of emotional intelligence and self-efficacy on the leadership effectiveness of the police.Research design, approach and method: This research adopted a quantitative approach to assess the relationship between emotional intelligence and self-efficacy as attributes of leadership effectiveness. A total of 107 police personnel in commanding positions made up the sample. The measuring instruments used were the Assessing Emotions Scale, the Self-efficacy Scale and the Multifactor Leadership Questionnaire (MLQ Form 5X.Main findings: The results confirmed a positive relationship between emotional intelligence and self-efficacy and leadership effectiveness. The correlations were significant at the 0.01 level (2-tailed.Practical/managerial implications: Emotional intelligence and self-efficacy should be considered as attributes during the selection of leaders in police organisations or used for developmental purposes to enhance these attributes in police leaders.Contribution/value-add: The insights gained from the findings may be used to guide the selection of future leaders in the policing environment, and they could also be used to establish future developmental programmes and research initiatives.

  12. What is biased efficacy? Defining the relationship between intrinsic efficacy and free energy coupling.

    Science.gov (United States)

    Onaran, H Ongun; Rajagopal, Sudarshan; Costa, Tommaso

    2014-12-01

    A G protein-coupled receptor (GPCR) is only biologically active when associated with a transduction protein, but it can also switch function by interacting with different types of transduction proteins. Biased agonism arises when the ligand induces the receptor to engage distinct transduction proteins with different efficacies. We briefly review the concept of ligand efficacy, from the classical empirical idea to the current mechanistic views of allosteric regulation in proteins. A combination of these theoretically distinct ideas and methodologies allows us to distinguish true ligand bias from divergences of signalling caused by the system. We also demonstrate a rigorous mathematical connection between the intrinsic efficacy of classical receptor theory and the energetic effect that makes a ligand capable of stabilizing receptor-transducer association in the ternary complex model. This relationship unifies different definitions of efficacy and provides a rational basis for quantifying biased agonism. PMID:25448316

  13. Effects of Korean red ginseng (Panax Ginseng Meyer) on bisphenol A exposure and gynecologic complaints: single blind, randomized clinical trial of efficacy and safety

    OpenAIRE

    Yang, Mihi; Lee, Ho-Sun; Hwang, Min-Woo; Jin, Mirim

    2014-01-01

    Background Korean red ginseng (KRG) is a processed ginseng from raw ginseng to enhance safety, preservation and efficacy, known having beneficial effects on women’s health due to its estrogen like function. While estrogen supplementation showed some modulation of endocrine disrupting chemicals, bisphenol A (BPA) has been focused as a potential endocrine disrupting chemical. In this study, we examined the efficacy and safety outcomes of KRG against BPA, focusing on female quality of life (QOL)...

  14. Teachers' self-efficacy, motivation adn teaching strategies - Auto-eficacia Docente, Motivación del Profesor y Estrategias de Enseñanza

    OpenAIRE

    Pedro Rosario; Rebeca Blas; Antonio Valle; Núñez, José C.; Susana Rodríguez

    2009-01-01

    According to previous research, teachers’ efficacy relating to teaching practices is highly dependent on the extent to which they are confident about their own capabilities to manage the new demands on their professional role. The present work aimed at: a) gathering information about the way teachers manage different aspects of self-efficacy (i.e., enhancing their instructional process in order to optimize their lessons and engage the students in the learning process), in order to identify ho...

  15. Efficacy of an exercise intervention for employees with work-related fatigue: study protocol of a two-arm randomized controlled trial

    OpenAIRE

    Vries, J.D. de; Hooff, M.L.M. van; Geurts, S.A.E.; Kompier, M.A.J.

    2015-01-01

    Background The aim of the current study is to evaluate the efficacy of an exercise intervention to reduce work-related fatigue. Exercise is a potentially effective intervention strategy to reduce work-related fatigue, since it may enhance employees’ ability to cope with work stress and it helps to detach from work. However, based on available research, no clear causal inferences regarding its efficacy can be made. This RCT therefore investigates whether exercise is effective in reducing work-...

  16. Efficacy of a brief manualized intervention Managing Cancer and Living Meaningfully (CALM) adapted to German cancer care settings: study protocol for a randomized controlled trial

    OpenAIRE

    Scheffold, Katharina; Philipp, Rebecca; Engelmann, Dorit; Schulz-Kindermann, Frank; Rosenberger, Christina; Oechsle, Karin; Härter, Martin; Wegscheider, Karl; Lordick, Florian; Lo, Chris; Hales, Sarah; Rodin, Gary; Mehnert, Anja

    2015-01-01

    Background Although psycho-oncological interventions have been shown to significantly reduce symptoms of anxiety and depression and enhance quality of life, a substantial number of patients with advanced cancer do not receive psycho-oncological interventions tailored to their individual situation. Given the lack of reliable data on the efficacy of psycho-oncological interventions in palliative care settings, we aim to examine the efficacy of a brief, manualized individual psychotherapy for pa...

  17. Young Men’s Shame about Their Desire for other Men Predicts Risky Sex and Moderates the Knowledge – Self-Efficacy Link

    OpenAIRE

    Park, Mina; Anderson, Janeane N.; Christensen, John L.; Miller, Lynn Carol; Appleby, Paul Robert; Read, Stephen John

    2014-01-01

    Background: Nationally, HIV incidence is rising rapidly among young (18–24 years old) men who have sex with men (YMSM). Knowledge of safer sex generally enhances self-efficacy for safer sex, an important predictor of safer-sex behaviors. Recent findings suggest that a strong negative social emotion (i.e., shame) increases YMSM’s sexual risk-taking. Unchangeable shame (e.g., desire for other men) might undermine (moderate) the link between knowledge and self-efficacy or between self-efficacy a...

  18. Enhancement of protective action of radioprotector

    International Nuclear Information System (INIS)

    The efficacy of radioprotector WR-2721 (300 mg/kg ip, 20 min before irradiation), alone or in combination with an extract of Ginkgo biloba (TeboninR) (17.5 mg/kg ip, 20 min before, and then 1 hr and 24 hr after irradiation), an extract of thymus (ThymolipR) (10 mg/kg sc, 24 hr before and 15 min after irradiation), herbal mitogen agrostemin (0.1 mg/kg ip. 24 before and immediately after irradiation) and calcium antagonist verapamil (1 mg/kg ip, immediately before irradiation), was studied in adult male Wistar rats irradiated by 9 Gy and 12 Gy of X-rays. It was established that above mentioned compounds, except wr-2721, failed to protect irradiated animals. Given in combination with WR-2721 only agrostemin and verapamil enhanced the efficacy of the protector. The combination with verapamil was more effective providing protection even in supralethal irradiated rats. (author)

  19. Assessing the immediate and maintained effects of hypnosis on self-efficacy and soccer wall-volley performance.

    Science.gov (United States)

    Barker, Jamie; Jones, Marc; Greenlees, Iain

    2010-04-01

    This study evaluated the effects of hypnosis on self-efficacy and soccer performance. Fifty-nine collegiate soccer players were randomly allocated to either a hypnosis (n = 30) or video attention-control group (n = 29). A pretest-posttest design with an additional 4-week follow-up was used. Self-efficacy was measured via a task-specific questionnaire comprising 10 items relating to good performance on a soccer wall-volley task. The hypnotic intervention comprised three sessions using ego-strengthening suggestions. The control group watched edited videos of professional soccer games. Results indicated that, following the intervention, the hypnosis group were more efficacious and performed better than the control group. These differences were also seen at the 4-week follow-up stage. Although changes in self-efficacy were associated with changes in performance, the effect of hypnosis on performance was not mediated by changes in self-efficacy. The study demonstrates that hypnosis can be used to enhance and maintain self-efficacy and soccer wall-volley performance. PMID:20479480

  20. Synergistic Antitumor Efficacy of Oncolytic Adenovirus Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Yue-min; QIAN Qi-jun; SONG San-tai; JIANG Ze-fei; ZHANG Qi; QU Yi-mei; SU Chang-qing; ZHAO Chuan-hua; LI Zhi-qiang; GE Fei-jiao

    2007-01-01

    Objective: Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods: We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results: In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion: We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.

  1. THE EFFECTS OF INTERVAL FEEDBACK ON THE SELF-EFFICACY OF NETBALL UMPIRES

    Directory of Open Access Journals (Sweden)

    Alison J. Mahoney

    2008-03-01

    Full Text Available The present study used quantitative and qualitative methods to explore the relationship between interval feedback and self-efficacy toward umpiring netball games. Grade "A" level umpires (n = 7 provided feedback to umpires (n = 40 under two conditions; 1 interval feedback given at the end of one tournament game (after 14 minutes and again at the end of a second consecutive game (after 28 minutes, and 2 feedback at the end of the game (after 28 minutes. Umpires in both conditions completed an Umpiring Self-Efficacy Questionnaire (USEQ which was a 14-item measure designed to assess factors relevant to netball umpire performance. Participants completed the USEQ immediately before game one, during the interval, and after a second game. Umpires also completed a feedback questionnaire which enabled them to reflect on the feedback received. A repeated measures factorial (time x feedback condition ANOVA indicated no significant interaction effect (F = 0.05, p > .05, and no main effect for condition (F = 0.06, p > .05 or time (F = 1.61, p > .05 for changes in self-efficacy. Although there were no significant effects, qualitative data alluded to aspects of feedback perceived to enhance umpire self-efficacy, thus identifying ways in which feedback might have a more consistent effect. Practical implications of the study in relation to verbal interval feedback are discussed

  2. Florida Preservice Agricultural Education Teachers' Mathematics Ability and Efficacy

    Science.gov (United States)

    Stripling, Christopher T.; Roberts, T. Grady

    2012-01-01

    The purpose of this study was to examine the mathematics ability and efficacy of Florida preservice agricultural education teachers. Results indicated that the preservice teachers were not proficient in solving agricultural mathematics problems. On the other hand, the preservice teachers were efficacious in personal teaching efficacy and personal…

  3. The Role of Means Efficacy When Predicting Creative Performance

    Science.gov (United States)

    Simmons, Aneika L.; Payne, Stephanie C.; Pariyothorn, Matthew M.

    2014-01-01

    According to the "Internal-External Efficacy model", self-efficacy is an insufficient explanation for self-regulated behavior because it ignores the influence of external resources. Applying this theory of motivation to the prediction of creative performance, the extent to which means efficacy or the belief in the utility of external…

  4. [Immunological surrogate endpoints to evaluate vaccine efficacy].

    Science.gov (United States)

    Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

    2015-12-01

    An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description. PMID:26887309

  5. White LEDs with limit luminous efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Lisitsyn, V. M.; Stepanov, S. A., E-mail: stepanovsa@tpu.ru; Yangyang, Ju [National Research Tomsk Polytechnic University, 30 Lenin Av., Tomsk, 634050 (Russian Federation); Lukash, V. S. [JSC Research Institute of Semiconductor Devices, 99a Krasnoarmeyskaja St., Tomsk, 634050 (Russian Federation)

    2016-01-15

    In most promising widespread gallium nitride based LEDs emission is generated in the blue spectral region with a maximum at about 450 nm which is converted to visible light with the desired spectrum by means of phosphor. The thermal energy in the conversion is determined by the difference in the energies of excitation and emission quanta and the phosphor quantum yield. Heat losses manifest themselves as decrease in the luminous efficacy. LED heating significantly reduces its efficiency and life. In addition, while heating, the emission generation output and the efficiency of the emission conversion decrease. Therefore, the reduction of the energy losses caused by heating is crucial for LED development. In this paper, heat losses in phosphor-converted LEDs (hereinafter chips) during spectrum conversion are estimated. The limit values of the luminous efficacy for white LEDs are evaluated.

  6. The Game Frame and Political Efficacy

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2012-01-01

    Several observational and experimental studies have confirmed the ‘spiral of cynicism’ hypothesis: the tendency of the news media to cover politics through a game frame, which focuses on political strategy instead of political issues, leads to cynicism about election campaigns and politicians among...... the electorate. However, such cynicism may in itself be somewhat inconsequential, and so this article suggests that we move beyond cynicism regarding specific electoral campaigns or politicians, and that we turn our attention towards political efficacy. This is done in an empirical study, which is...... based on a survey among the electorate and a content analysis of political coverage in newspapers. The study shows that exposure to the game frame is indeed associated with lower levels of internal efficacy, even when controlling for potentially confounding variables....

  7. Medical students’ self-efficacy in problem-based learning and its relationship with self-regulated learning

    OpenAIRE

    Demirören, Meral; Turan, Sevgi; Öztuna, Derya

    2016-01-01

    Background: Problem-based learning (PBL) is most commonly used in medical education to enhance self-regulated learning (SRL) skills. Self-efficacy beliefs affect students’ motivation through self-regulatory processes. The purpose of this study is to examine the relationship between medical students’ self-reported SRL skills and their self-efficacy in PBL.Methods: A cross-sectional study was conducted with second (286; 83.1%) and third (275; 80.2%) year students at the Ankara University School...

  8. SAFETY AND EFFICACY OF PAEDIATRIC PCNL

    OpenAIRE

    Jagadeeshwar; Ravi; Bhagawan; Rama Murthy; Ravichandar; Mallikarjun; Santosh; Narendra

    2014-01-01

    AIMS AND OBJECTIVES OF THE STUDY: To evaluate the indications of PCNL in children with age from 1to14yrs, identify the complications, treatment of complications, and prevention of complications and to evaluate the safety & efficacy of management of kidney stones in children by PCNL. MATERIAL & METHODS: Study period includes October 2010 to February 2013. 28 cases of renal stone in paediatric age group were admitted in our Hospital and evaluated for size of the stone, numbe...

  9. The Practical Evaluation of DNA Barcode Efficacy*

    OpenAIRE

    Spouge, John L.; Mariño-Ramírez, Leonardo

    2012-01-01

    This chapter describes a workflow for measuring the efficacy of a barcode in identifying species. First, assemble individual sequence databases corresponding to each barcode marker. A controlled collection of taxonomic data is preferable to GenBank data, because GenBank data can be problematic, particularly when comparing barcodes based on more than one marker. To ensure proper controls when evaluating species identification, specimens not having a sequence in every marker database should be ...

  10. Primary School Teachers’ Belief of Efficacy

    OpenAIRE

    YILMAZ, Kürşad; Bökeoğlu, Ömay Çokluk

    2008-01-01

    The purpose of the present study is to determineefficacy belief of primary school teachers. In the survey model study,“Teacher Efficacy Scale” was used to gather data. The scaledeveloped by Woolfolk and Hoy (1990) was adapted to Turkish by theauthors. The scale includes 22 likert type items to determine efficacybeliefs of teachers. Study group of the research consists of 250teachers who work in primary schools in Ankara city centre. In thestudy, percentage, frequency, arithmetic average, t te...

  11. Social and emotional self-efficacy at work.

    Science.gov (United States)

    Loeb, Carina; Stempel, Christiane; Isaksson, Kerstin

    2016-04-01

    Research has shown that self-efficacy is often one of the most important personal resources in the work context. However, because this research has focused on cognitive and task-oriented self-efficacy, little is known about social and emotional dimensions of self-efficacy at work. The main aim of the present study was to investigate social and emotional self-efficacy dimensions at work and to compare them to a cognitive and task-oriented dimension. Scales to measure social and emotional self-efficacy at work were developed and validated and found to be well differentiated from the cognitive task-oriented occupational self-efficacy scale. Confirmatory factor analyses of data from 226 Swedish and 591 German employees resulted in four separate but correlated self-efficacy dimensions: (1) occupational; (2) social; (3) self-oriented emotional; and (4) other-oriented emotional. Social self-efficacy explained additional variance in team climate and emotional self-efficacy in emotional irritation and emotional exhaustion, over and above effects of occupational self-efficacy. Men reported higher occupational self-efficacy, whereas social and emotional self-efficacy revealed no clear gender differences. The scales have strong psychometric properties in both Swedish and German language versions. The positive association between social self-efficacy and team climate, and the negative relationships between self-oriented emotional self-efficacy and emotional irritation and emotional exhaustion may provide promising tools for practical applications in work settings such as team-building, staff development, recruitment or other training programs aiming for work place health promotion. The next step will be to study how social and emotional self-efficacy relate to leadership, well-being and health over time. PMID:26882457

  12. Exploring the Relationship between Teaching Efficacy and Cultural Efficacy of Novice Science Teachers in High-Needs Schools

    Science.gov (United States)

    Moseley, Christine; Bilica, Kimberly; Wandless, Ana; Gdovin, Ralph

    2014-01-01

    This qualitative case study sought to investigate what relationship exists between teaching efficacy and cultural efficacy of novice science teachers in high-needs, high-minority urban schools. One major theme--the importance of establishing positive teacher-student relationships--surrounding teaching efficacy in the context of cultural efficacy…

  13. Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy

    Science.gov (United States)

    2014-05-05

    Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  14. Contrast-enhanced endoscopic ultrasonography

    Institute of Scientific and Technical Information of China (English)

    Nischita K Reddy; Ana Maria Ioncic(a); Adrian S(a)ftoiu; Peter Vilmann; Manoop S Bhutani

    2011-01-01

    Contrast agents are increasingly being used to characterize the vasculature in an organ of interest,to better delineate benign from malignant pathology and to aid in staging and directing therapeutic procedures.We review the mechanisms of action of first,second and third generation contrast agents and their use in various endoscopic procedures in the gastrointestinal tract.Various applications of contrast-enhanced endoscopic ultrasonography include differentiating benign from malignant mediastinal lymphadenopathy,assessment of depth of invasion of esophageal,gastric and gall bladder cancers and visualization of the portal venous system and esophageal varices.In addition,contrast agents can be used to differentiate pancreatic lesions.The use of color Doppler further increases the ability to diagnose and differentiate various pancreatic malignancies.The sensitivity of power Doppler sonography to depict tumor neovascularization can be increased by contrast agents.Contrast-enhanced harmonic imaging is a useful aid in identifying the tumor vasculature and studying pancreatic microperfusion.In the future,these techniques could potentially be used to quantify tumor perfusion,to assess and monitor the efficacy of antiangiogenic agents,to assist targeted drug delivery and allow molecular imaging.

  15. The Efficacy of High-Intensity Focused Ultrasound (HIFU) in Advanced Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    Bo Xie; Jiajun Ling; Weiming Zhang; Xueqin Huang; Jihua Zhen; Yanzhe Huang

    2008-01-01

    OBJECTIVE To observe the efficacy of high-intensity focused ultrasound (HIFU)in the treatment of late-stage pancreatic cancer.METHODS Sixteen patients with advanced pancreatic cancer received HIFU therapy.Evaluation of efficacy was made on the basis of changes in clinical symptoms and variations in the tumor echo and size.RESULTS Clinical symptoms such as pain were significantly alleviated,echo of the tumor was enhanced with B-US and the quality of life such as eating,sleeping and mental status was markedly improved;no serious complications were observed.CONCLUSION The use of HIFU in the treatment of advanced pancreatic cancer is feasible and safe.It is effective in killing the carcinoma cells and alleviaring pain.This technique may offer non-invasive therapy for the treatment of patients with late-stage pancreatic cancer.

  16. Preconditioning Vaccine Sites for mRNA-Transfected Dendritic Cell Therapy and Antitumor Efficacy.

    Science.gov (United States)

    Batich, Kristen A; Swartz, Adam M; Sampson, John H

    2016-01-01

    Messenger RNA (mRNA)-transfected dendritic cell (DC) vaccines have been shown to be a powerful modality for eliciting antitumor immune responses in mice and humans; however, their application has not been fully optimized since many of the factors that contribute to their efficacy remain poorly understood. Work stemming from our laboratory has recently demonstrated that preconditioning the vaccine site with a recall antigen prior to the administration of a dendritic cell vaccine creates systemic recall responses and resultantly enhances dendritic cell migration to the lymph nodes with improved antitumor efficacy. This chapter describes the generation of murine mRNA-transfected DC vaccines, as well as a method for vaccine site preconditioning with protein antigen formulations that create potent recall responses. PMID:27076169

  17. An active ingredient of Cat's Claw water extracts identification and efficacy of quinic acid.

    Science.gov (United States)

    Sheng, Yezhou; Akesson, Christina; Holmgren, Kristin; Bryngelsson, Carl; Giamapa, Vincent; Pero, Ronald W

    2005-01-15

    Historic medicinal practice has defined Cat's Claw, also known as Una de Gato or Uncaria tomentosa, as an effective treatment for several health disorders including chronic inflammation, gastrointestinal dysfunction such as ulcers, tumors and infections. The efficacy of Cat's Claw was originally believed, as early as the 1960s, to be due to the presence of oxindole alkaloids. However, more recently water-soluble Cat's Claw extracts were shown not to contain significant amounts of alkaloids (<0.05%), and yet still were shown to be very efficacious. Here we characterize the active ingredients of a water-soluble Cat's Claw extract called C-Med-100 as inhibiting cell growth without cell death thus providing enhanced opportunities for DNA repair, and the consequences thereof, such as immune stimulation, anti-inflammation and cancer prevention. The active ingredients were chemically defined as quinic acid esters and could also be shown to be bioactive in vivo as quinic acid. PMID:15619581

  18. A comprehensive survey of the relationship between self-efficacy and performance for the governmental auditors.

    Science.gov (United States)

    Su, Jau-Ming; Lee, Shue-Ching; Tsai, Sang-Bing; Lu, Tzu-Li

    2016-01-01

    As governmental auditing is involved in evaluating the legitimacy, economy, efficiency, and effectiveness of how the various administrative branches use their allocated resources to optimize the government's functions, it is expected that the performance of the auditors in charge are strongly influenced by their respective qualities such as self-efficacy and experience, etc. To further understand the factors that may enhance their performance and to ultimately provide practical recommendations for the audit authorities, we have surveyed about 50 % of all the governmental auditors in Taiwan. The result showed that any auditing experience and professionalization do positively influence the professional awareness, and acquired knowledge and skillset of an auditor can effectively improve his or her professional judgment. We also found that perceived ability, problem-solving skills, and resource sharing may significantly impact any performance involved. Our study provides a workable management guidelines for strengthening the self-efficacy of audit authorities in Taiwan. PMID:27186472

  19. Immunotherapy of Metastases Enhances Subsequent Chemotherapy

    Science.gov (United States)

    Hanna, Michael G.; Key, Marc E.

    1982-07-01

    In many multimodal therapies of cancer, postsurgical chemotherapy is administered before immunotherapy for treatment of micrometastatic disease. This sequence may not be the most efficacious. Experiments in which strain 2 guinea pigs bearing syngeneic L10 hepatocarcinomas were given immunotherapy showed that infiltrating immune effector cells not only were tumoricidal but disrupted the characteristically compact structure of metastatic foci. When cytotoxic drugs were administered at the peak of this inflammatory response, the survival rate of the guinea pigs increased significantly. We conclude that postsurgical immunotherapy can enhance the effect of cytotoxic drugs administered subsequently.

  20. Engineering Professional Development: Elementary Teachers' Self-efficacy and Sources of Self-efficacy

    Science.gov (United States)

    Webb, Donna Louise

    Currently, STEM (science, technology, engineering, and mathematics) is a popular buzz word in P-12 education as it represents a means to advance American competitiveness in the global economy. Proponents of the engineering component of STEM advocate additional benefits in teaching engineering, such as its capacity to engage students in collaboration, and to apply critical thinking, systems thinking, negotiation, and communication skills to solve real-life contextual problems. Establishing a strong foundation of engineering knowledge at a young age will provide students with internal motivation as it taps into their curiosity toward how things work, and it also prepares them for secondary science courses. Successful STEM education is often constrained by elementary teachers' low perception of self-efficacy to teach science and engineering. Elementary teachers with low self-efficacy in science are more likely to spend less instructional time teaching science, which suggests that teachers with little to no training in engineering might avoid teaching this topic. Therefore, the purpose of this study was twofold: (a) to examine the effects of engineering professional development on elementary (K-6) teachers' content and pedagogical content knowledge (PCK) and perceptions of self-efficacy to teach engineering, and (b) to identify and explain sources influencing self-efficacy. Professional development was conducted in a metropolitan area in the Pacific Northwest. Results revealed that after the engineering professional development, teachers experienced statistically significant gains in content, PCK, and self-efficacy to teach engineering. Increases in self-efficacy were mainly attributed to mastery experiences and cultivation of a growth mindset by embracing the engineering design process.

  1. The efficacy of surfactant replacement therapy in the growth restricted preterm infant: what is the evidence?

    Directory of Open Access Journals (Sweden)

    Atul eMalhotra

    2014-10-01

    Full Text Available Background: Surfactant replacement therapy (SRT is an integral part of management of preterm surfactant deficiency (respiratory distress syndrome, RDS. Its role in the management of RDS has been extensively studied. However its efficacy in the management of lung disease in preterm infants born with intrauterine growth restriction (IUGR has not been systematically studied.Objective: To evaluate the efficacy of exogenous surfactant replacement therapy in the management of preterm IUGR lung disease. Methods: A systematic search of all available randomised clinical trials (RCT of surfactant replacement therapy in preterm IUGR infants was done according to the standard Cochrane collaboration search strategy. Neonatal respiratory outcomes were compared between the preterm IUGR and appropriately-grown for gestational age (AGA preterm infant populations in eligible studies. Results: No study was identified which evaluated the efficacy or responsiveness of exogenous surfactant replacement therapy in preterm IUGR infants as compared to preterm AGA infants. The only study identified through the search strategy used small for gestational age (SGA; defined as less than 10th centile for birth weight as a proxy for IUGR. The RCT evaluated the efficacy or responsiveness of SRT in preterm SGA group as compared to AGA infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary air leaks and days on the ventilator did not differ between both groups. However, the requirement for prolonged nasal CPAP (p< 0.001, supplemental oxygen therapy (p <0.01 and the incidence of bronchopulmonary dysplasia at 28 days and 36 weeks (both p<0.01 was greater in SGA infants. Discussion: There is currently insufficient data available to evaluate the efficacy of SRT in preterm IUGR lung disease. A variety of research strategies will be needed to enhance our understanding of the role and rationale for use of surfactant replacement therapy in preterm

  2. The relationship of task self-efficacy and role efficacy beliefs to role performance in Spanish youth soccer.

    Science.gov (United States)

    Bray, Steven R; Balaguer, Isabel; Duda, Joan L

    2004-05-01

    The aim of this study was to examine the relationship between role efficacy and role performance after controlling for the effects of task self-efficacy. Two hundred and ninety-five Spanish youth soccer players from 20 teams completed self-report measures of task self-efficacy, role efficacy and role performance at the mid-point of a competitive season. The 20 team coaches also provided ratings of each of their players' role performances at mid-season. Consistent with hypotheses, bivariate correlations showed task self-efficacy and role efficacy were positively related to role performance ratings. Hierarchical regression analyses revealed that role efficacy contributed significantly to the prediction of athletes' ratings of role performance after controlling for task self-efficacy. Role efficacy also explained significant variation in the prediction of coach ratings; however, the effects were less dramatic and inconsistent. Our results support self-efficacy theory and reinforce the value of assessing efficacy beliefs representing behaviours carried out both independently and interdependently for the prediction of role performance within team environments. Future research directions are proposed. PMID:15160596

  3. Trauma Coping Self-Efficacy: A Context Specific Self-Efficacy Measure for Traumatic Stress

    OpenAIRE

    Benight, Charles C.; Shoji, Kotaro; Lori E. James; Waldrep, Edward E.; Delahanty, Douglas L.; Cieslak, Roman

    2015-01-01

    The psychometric properties of a Trauma Coping Self-Efficacy (CSE-T) scale that assesses general trauma-related coping self-efficacy perceptions were assessed. Measurement equivalence was assessed using several different samples: hospitalized trauma patients (n1 = 74, n2 = 69, n3 = 60), three samples of disaster survivors (n1 = 273, n2 = 227, n3 = 138), and trauma exposed college students (N = 242). This is the first multi-sample evaluation of the psychometric properties for a general trauma-...

  4. Cognitive Enhancers for Facilitating Drug Cue Extinction: Insights from Animal Models

    OpenAIRE

    Nic Dhonnchadha, Bríd Áine; Kantak, Kathleen M.

    2011-01-01

    Given the success of cue exposure (extinction) therapy combined with a cognitive enhancer for reducing anxiety, it is anticipated that this approach will prove more efficacious than exposure therapy alone in preventing relapse in individuals with substance use disorders. Several factors may undermine the efficacy of exposure therapy for substance use disorders, but we suspect that neurocognitive impairments associated with chronic drug use are an important contributing factor. Numerous insigh...

  5. Enhanced Antidepressant-Like Effects of Electroacupuncture Combined with Citalopram in a Rat Model of Depression

    OpenAIRE

    Yang, Jian; Pei, Yu; Pan, Yan-Li; Jia, Jun; Shi, Chen; Yu, Yan; Deng, Jia-Hui; Li, Bo; Gong, Xiao-Li; Wang,Xuan; Xiao-min WANG; Ma, Xin

    2013-01-01

    Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we ...

  6. Dextropropoxyphene: safety and efficacy in older patients.

    Science.gov (United States)

    Goldstein, David J; Turk, Dennis C

    2005-01-01

    Dextropropoxyphene, alone or in combination with acetaminophen (paracetamol), is among the most frequently prescribed opioid analgesics in the elderly in the US despite the American Geriatric Society recommendation that its use should be restricted. However, this recommendation is based on expert opinion in an apparent absence of data. Accordingly, we conducted a literature search which identified nine studies that reported efficacy and safety data for dextropropoxyphene in predominantly older patients (> or = 55 years of age). These studies were evaluated to assess the efficacy and safety of dextropropoxyphene compared with other opioids and to evaluate whether safety and tolerability differed in older versus younger patients. The efficacy of dextropropoxyphene appeared to be similar to that of other analgesics, and its safety was comparable to that of other opioid analgesics. Although the adverse event profile suggests that elderly patients might have more frequent gastrointestinal and CNS complaints than younger patients treated with dextropropoxyphene, the frequency of reports appears similar to that of other opioids. The incidences of dizziness and somnolence were not significantly greater in older patients (1-2% and 0-21%, respectively) than in younger patients (8% and 13%, respectively). The absence of clinical studies directly addressing the safety and tolerability of dextropropoxyphene in elderly patients (>65 years of age) versus younger patients encumbers assessment of the validity of restricting its use in the elderly. Careful outcomes research is needed to assess the effectiveness and safety of dextropropoxyphene in older patients and to develop evidence-based risk/benefit prescribing criteria for use of this drug in this age group. PMID:15903354

  7. What is the academic efficacy of podcasting?

    DEFF Research Database (Denmark)

    Heilesen, Simon

    2010-01-01

    performance, indications of the efficacy of podcasting are as yet fairly weak - admitting for a general lack of longitudinal studies. Still, podcasting does seem to have a general positive impact on the academic environment. One such effect is opening up for experimentation with known forms of teaching......Podcasting may be an answer to some of the challenges to higher education to modernize, to open up, and to develop a competitive edge. However, over the years there have been many high claims for new technology, and not all of them have been redeemed. In terms of academic performance, it may...

  8. Validity and efficacy of the labor contract

    Directory of Open Access Journals (Sweden)

    Jorge Toyama

    2012-12-01

    Full Text Available The validity and efficacy of the labor contract as well as cases of nullity and defeasibility import an analysis of scopes of the supplementary application of Civil Code taking into account the peculiarities of Labor Law. Labor contract, while legal business has as regulatory framework to the regulations of Civil Code but it is necessary to determine, in each case, whether to apply fully this normative body, or modulate its supplemental application, or simply conclude that it doesn’t result compatible its regulation due to the special nature of labor relations. Specifically, this issue will be analyzed from cases of nullity and defeasibility of the labor contract.

  9. The Efficacy of DO-178B

    OpenAIRE

    Daniels, Dewi

    2014-01-01

    DO-178B was based on the consensus of the avionic software community as it existed in 1992. Twenty two years after publication, we have no publically available experimental data as to its efficacy. It appears to work extremely well, since there have been no hull loss accidents in passenger service ascribed to software failure. This is a comforting and surprising result. However, if we don't know why DO-178B works so well, there is a danger that we could stop doing something that really matter...

  10. Anthelmintic efficacy fenbendazole paste in equines.

    Science.gov (United States)

    Malan, F S; Reinecke, R K; Scialdo, R C

    1981-06-01

    A single oral dose of fenbendazole (FBZ) paste at 7,5 mg/kg body mass was given to 5 horses. It was highly effective against adults of the following genera: Cyathostomum, Cylicostephanus, Cylicondontophorus, Poteriostomum, Cylicocyclus, Triodontophorus, Oesophagodontus (and other genera belonging to the subfamily Cyathostominae). Similarly, high efficacy was obtained against the adults of the following species: Oxyuris equi, Strongylus vulgaris, Strongylus equinus and Probstmayria vivipara. These results were confirmed in 12 horses and in addition FBZ at 7,5 mg/kg was highly effective against Parascaris equorum, Craterostomum and Gyalocephalus. PMID:7277372

  11. Sulfasalazine efficacy and tolerability in rheumatic diseases

    Directory of Open Access Journals (Sweden)

    V. V. Badokin

    2005-08-01

    Full Text Available Sulfasalazine is one of the main disease modifying drugs for the treatment of chronic inflammatory joint and spine diseases. The article describes mechanism of action of sulfasalazine and its main metabolites. Detailed information about anti-inflammatory and immunosuppressive action of the drug is presented. Results of many studies of sulfasalazine efficacy in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis are discussed from the evidence based medicine point of view. Data on sulfasalazine tolerability and safety are presented with separate discussion of hypersensitivity and dose-dependent adverse reactions so as their treatment and prophylaxis.

  12. Enteral feeding pumps: efficacy, safety, and patient acceptability

    Directory of Open Access Journals (Sweden)

    White H

    2014-08-01

    Full Text Available Helen White, Linsey King Nutrition and Dietetic Group, School of Health and Wellbeing, Faculty Health and Social Science, Leeds Metropolitan University, Leeds, United Kingdom Abstract: Enteral feeding is a long established practice across pediatric and adult populations, to enhance nutritional intake and prevent malnutrition. Despite recognition of the importance of nutrition within the modern health agenda, evaluation of the efficacy of how such feeds are delivered is more limited. The accuracy, safety, and consistency with which enteral feed pump systems dispense nutritional formulae are important determinants of their use and acceptability. Enteral feed pump safety has received increased interest in recent years as enteral pumps are used across hospital and home settings. Four areas of enteral feed pump safety have emerged: the consistent and accurate delivery of formula; the minimization of errors associated with tube misconnection; the impact of continuous feed delivery itself (via an enteral feed pump; and the chemical composition of the casing used in enteral feed pump manufacture. The daily use of pumps in delivery of enteral feeds in a home setting predominantly falls to the hands of parents and caregivers. Their understanding of the use and function of their pump is necessary to ensure appropriate, safe, and accurate delivery of enteral nutrition; their experience with this is important in informing clinicians and manufacturers of the emerging needs and requirements of this diverse patient population. The review highlights current practice and areas of concern and establishes our current knowledge in this field. Keywords: nutrition, perceptions, experience

  13. Change Management in Financial Efficacy of Banks: Evidence from Oman

    Directory of Open Access Journals (Sweden)

    Ravi Thirumalaisamy

    2014-01-01

    Full Text Available Banking and financial sector assume a crucial role in enhancing economic development. During 1990s, when GCC countries underwent major economic reforms, the private sector had to play a leading role by participating in the economic development activities such as designing and implementing private programs in which the private sector can significantly contribute. Since the role of private sector has expanded, their financial requirements have increased. This gap was largely filled in by the banking sector for capital market has not been so effective in the Gulf region. Thus, Banking sector reforms have forced the banks in Gulf region to be more focused on satisfying customers developing new operating models, defining new business strategies to achieve operational efficiency in the changing environment. When it comes to Oman, the banking system is sound and efficient. A major challenge being faced by the banks in Oman is to manage the operational and strategic changes that are increasingly taking place after 1990 when major economic reforms were introduced. Efficient change management is the driving and resisting force for achieving the bench mark target in all functions of banks. The purpose of the study is to measure the financial efficacy of commercial banks in Oman after 1990s in the process of their way of handling the changes.

  14. Efficacy of histotripsy combined with rt-PA in vitro

    Science.gov (United States)

    Bader, Kenneth B.; Haworth, Kevin J.; Shekhar, Himanshu; Maxwell, Adam D.; Peng, Tao; McPherson, David D.; Holland, Christy K.

    2016-07-01

    Histotripsy, a form of therapeutic ultrasound that uses the mechanical action of microbubble clouds for tissue ablation, is under development to treat chronic deep vein thrombosis (DVT). We hypothesize that combining thrombolytic agents with histotripsy will enhance clot lysis. Recombinant tissue plasminogen activator (rt-PA) and rt-PA-loaded echogenic liposomes that entrain octafluoropropane microbubbles (OFP t-ELIP) were used in combination with highly shocked histotripsy pulses. Fully retracted porcine venous clots, with similar features of DVT occlusions, were exposed either to histotripsy pulses alone (peak negative pressures of 7–20 MPa), histotripsy and OFP t-ELIP, or histotripsy and rt-PA. Microbubble cloud activity was monitored with passive cavitation imaging during histotripsy exposure. The power levels of cavitation emissions from within the clot were not statistically different between treatment types, likely due to the near instantaneous rupture and destruction of OFP t-ELIP. The thrombolytic efficacy was significantly improved in the presence of rt-PA. These results suggest the combination of histotripsy and rt-PA could serve as a potent therapeutic strategy for the treatment of DVT.

  15. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    Science.gov (United States)

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

    2015-07-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied. PMID:26393186

  16. Adapting Computer Programming Self-Efficacy Scale and Engineering Students' Self-Efficacy Perceptions

    Science.gov (United States)

    Korkmaz, Özgen; Altun, Halis

    2014-01-01

    Students might have different type and different level of perceptions: Positive or negative perceptions on programming; a perception on benefit of programming, perceptions related to difficulties of programming process etc. The perception of student on their own competence is defined as self-efficacy. Based on the discussions reported in…

  17. Increasing the Efficacy of Oncolytic Adenovirus Vectors

    Directory of Open Access Journals (Sweden)

    William S. M. Wold

    2010-08-01

    Full Text Available Oncolytic adenovirus (Ad vectors present a new modality to treat cancer. These vectors attack tumors via replicating in and killing cancer cells. Upon completion of the vector replication cycle, the infected tumor cell lyses and releases progeny virions that are capable of infecting neighboring tumor cells. Repeated cycles of vector replication and cell lysis can destroy the tumor. Numerous Ad vectors have been generated and tested, some of them reaching human clinical trials. In 2005, the first oncolytic Ad was approved for the treatment of head-and-neck cancer by the Chinese FDA. Oncolytic Ads have been proven to be safe, with no serious adverse effects reported even when high doses of the vector were injected intravenously. The vectors demonstrated modest anti-tumor effect when applied as a single agent; their efficacy improved when they were combined with another modality. The efficacy of oncolytic Ads can be improved using various approaches, including vector design, delivery techniques, and ancillary treatment, which will be discussed in this review.

  18. VIBE: Evaluation of Ibandronate Efficacy - Original Investigation

    Directory of Open Access Journals (Sweden)

    J-Y Reginster

    2008-12-01

    Full Text Available No prospective head-to-head trials comparing the fracture efficacy of the currently marketed weekly and monthly bisphosphonates have been conducted. Due to the large sample size such studies would require to reliably detect differences in fracture risk and the associated high costs, they are considered to be impractical. Whilst providing the highest level of evidence, clinical trials also have inherent limitations. Patients are selected by a number of criteria and therefore usually do not represent the normal patient population. Also due to a protocol, normal clinical practice is usually not reflected. In contrast, database studies allow the assessment of treatments in normal clinical practice. Whilst observational studies have limitations owing to more confounding variables, they do have an important place in evidence-based medicine (especially in the absence of prospective clinical trials, and if well-designed can give some indications regarding the comparative efficacy of osteoporosis therapies in real-world clinical practice. (From the World of Osteoporosis 2008;14: 62-5

  19. Self-efficacy moderation and mediation roles on BPSD and social support influences on subjective caregiver burden in Chinese spouse caregivers of dementia patients.

    Science.gov (United States)

    Zhang, Shuying; Guo, Qihao; Edwards, Helen; Yates, Patsy; Li, Chunbo

    2014-06-16

    ABSTRACT Background: This study aims to explore moderation and mediation roles of caregiver self-efficacy between subjective caregiver burden and (a) behavioral and psychological symptoms (BPSD) of dementia; and (b) social support. Methods: A cross-sectional study with 137 spouse caregivers of dementia patients was conducted in Shanghai. We collected demographic information for the caregiver-patient dyads, as well as information associated with dementia-related impairments, caregiver social support, caregiver self-efficacy, and SF-36. Results: Multiple regression analysis showed that caregiver self-efficacy was a moderator both between BPSD and subjective caregiver burden, and social support and subjective caregiver burden. Results also showed a partial mediation effect of caregiver self-efficacy on the impact of BPSD on subjective caregiver burden, and a mediation effect of social support on subjective caregiver burden. Caregiver self-efficacy and subjective burden significantly influenced BPSD and social support. Conclusion: Caregiver self-efficacy played an important role in the paths by which the two factors influenced subjective burden. Enhancing caregiver self-efficacy for symptom management (particularly BPSD) can be an essential strategy for determining interventions to support dementia caregivers in China, and possibly in other countries. PMID:24932533

  20. Positive Impacts of Modeling Instruction on Self-Efficacy

    Science.gov (United States)

    Sawtelle, Vashti; Brewe, Eric; Kramer, Laird H.

    2010-10-01

    Analysis of the impact of Modeling Instruction (MI) on the sources of self-efficacy for students in Introductory Physics 1 will be presented. We measured self-efficacy through a quantitative diagnostic (SOSESC) developed by Fencl and Scheel [1] to investigate the impact of instruction on the sources of self-efficacy in all introductory physics classes. We collected both pre- semester data and post-semester data, and evaluated the effect of the classroom by analyzing the shift (Post-Pre). At Florida International University, a Hispanic-serving institution, we find that traditional lecture classrooms negatively impact the self-efficacy of all students, while the MI courses had no impact for all students. Further, when disaggregating the data by gender and sources of self-efficacy, we find that Modeling Instruction positively impacted the Verbal Persuasion source of self-efficacy for women. This positive impact helps to explain high rates of retention for women in the MI classes.

  1. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    Directory of Open Access Journals (Sweden)

    Rianne A. de Kleine

    2013-10-01

    Full Text Available There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD. Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: D-cycloserine, MDMA, hydrocortisone, and propranolol.

  2. Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance in a Discordant Sensory Environment

    Science.gov (United States)

    Temple, David R.; De Dios, Yiri E.; Layne, Charles S.; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.

    2016-01-01

    Astronauts exposed to microgravity face sensorimotor challenges incurred when readapting to a gravitational environment. Sensorimotor Adaptability (SA) training has been proposed as a countermeasure to improve locomotor performance during re-adaptation, and it is suggested that the benefits of SA training may be further enhanced by improving detection of weak sensory signals via mechanisms such as stochastic resonance when a non-zero level of stochastic white noise based electrical stimulation is applied to the vestibular system (stochastic vestibular stimulation, SVS). The purpose of this study was to test the efficacy of using SVS to improve short-term adaptation in a sensory discordant environment during performance of a locomotor task.

  3. Cognitive behavioral strategies in athletic performance enhancement.

    Science.gov (United States)

    Meyers, A W; Whelan, J P; Murphy, S M

    1996-01-01

    While we might debate the role of sport in our culture, its influence is certainly pervasive. Each day millions of Americans engage in some form of competition, training, or physical exercise. Such popularity and the value our culture places on competition have made sport a valid area of psychological inquiry. Within the cognitive behavioral model, sport psychology and, specifically, athletic performance enhancement have experienced vigorous growth over the past two decades. Behavior change strategies familiar to most cognitive behaviorists form the core of virtually all athletic performance enhancement interventions. Goal setting, imagery or mental rehearsal, relaxation training, stress management, self-monitoring, self-instruction, cognitive restructuring, and modeling interventions dominate this literature. Our examination of these performance enhancement programs, both through a qualitative review and the Whelan et al. (1989) meta-analysis, supports the efficacy of cognitive behavioral interventions for the enhancement of sport performance. First, the average effect size across the empirical literature indicates that these interventions are reliably effective. Furthermore, this positive result is observed across variations in treatment conditions, control conditions, and across different types of dependent measures. Evidence on goal setting, imagery, arousal management, cognitive self-regulation, and packaged programs specifically support the behavior change efficacy of these interventions. These findings are encouraging, but much work needs to be done. Few investigators cited in this review attend to crucial internal and external validity issues. Attention to treatment integrity, including training of behavior change agents, verification of intervention implementation, and verification of reception of the treatment, is sorely lacking. Psychological skill development and its relationship to performance improvements are rarely checked. Now that cognitive

  4. Social Capital, Socioeconomic Status and Self-efficacy

    OpenAIRE

    Jing Han; Xiaoyuan Chu; Huicun Song; Yuan Li

    2015-01-01

    This study internalized social capital on the basis of traditional study of the influence of economic factors on self-efficacy, and studied the relationship among the family socio-economic status, social capital and self-efficacy. Based on the theoretical analysis, with first-hand data collection and using multiple regression models, the paper studied the intermediate effect of social capital in the relationship between the socioeconomic status and self-efficacy. We draw on the following conc...

  5. VET efficacy : evaluation of factors in the workplace training

    OpenAIRE

    Pineda i Herrero, Pilar; Quesada Pallarès, Carla; Mas Torelló, Óscar; Espona Barcons, Berta; Garcia Castaño, Natàlia

    2012-01-01

    Training in the workplace is a key part of VET studies because allows students to develop their skills in a work setting, and gives important information about how well VET studies prepare skilled workers. However, there is little information about factors that influence the efficacy of training in the workplace. Our aim is to evaluate the efficacy of training in the workplace, through the factors that influence training efficacy. We applied a questionnaire of 57 items (5-point Likert scale),...

  6. Two Faces of Mobile Shopping: Self-Efficacy and Impulsivity

    OpenAIRE

    Thaemin Lee; Cheol Park; Jongkun Jun

    2014-01-01

    This study examines the positive and negative effects of mobile shopping. It identifies and tests the antecedents and consequences of self-efficacy and impulse buying that result from mobile shopping. The results reveal that perceived convenience, perceived ease of response, and perceived control significantly affect self-efficacy and impulse buying. In addition, the results demonstrate that significant relationships exist between self-efficacy and satisfaction, and impulse buying and regret....

  7. Assessing Perceived Empathic and Social Self-Efficacy Across Countries

    OpenAIRE

    Di Giunta, Laura; Eisenberg, Nancy; Kupfer, Anne; Steca, Patrizia; Tramontano, Carlo; Caprara, Gian Vittorio

    2010-01-01

    The Perceived Empathic Self-Efficacy Scale (PESE) and the Perceived Social Self-Efficacy Scale (PSSE) were developed to assess, respectively, individuals’ self-efficacy beliefs regarding both empathic responding to others’ needs or feelings and managing interpersonal relationships. In this study of young adults, a unidimensional factorial structure of both scales was found in Italy, the United States, and Bolivia. Complete invariance at the metric level and partial invariance at the scalar le...

  8. Long-term persistence of zoster vaccine efficacy

    OpenAIRE

    Johnson, GR; Zhang, Jh; Betts, R.; Gelb, L; Guatelli, JC; Harbecke, R; Pachucki, C.; Keay, S; Marques, A; Toney, J.; Boardman, K; Su, SC; Li, X.; Chan, ISF; Parrino, J

    2015-01-01

    Background. The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. ...

  9. Massage Efficacy Beliefs for Muscle Recovery from a Running Race

    OpenAIRE

    Moraska, Albert

    2013-01-01

    Background Belief in efficacy of CAM therapies has been sparsely reported and may be different than reported use of the therapy. Purpose The aim of this study was to identify efficacy beliefs of massage for muscle recovery following a 10-km running race. Setting Finish zone of a 10-km race. Research Design Participants completed a brief survey regarding running race characteristics, prior use of massage, and belief in efficacy of massage regarding muscle recovery from the race. Participants T...

  10. Efficacy of virtual reality-based balance training versus the Biodex balance system training on the body balance of adults

    OpenAIRE

    Ibrahim, Manal S.; Mattar, Ayman G.; Elhafez, Salam M.

    2016-01-01

    [Purpose] This study investigated efficacy of virtual reality (VR)-based balance training on enhancing balance and postural reactions of adults as a low-cost new modality compared to the established Biodex Balance System (BBS). [Subjects] Thirty normal adults of both genders were divided randomly into two equal-sized experimental groups of 15: BBS balance training and VR balance training. [Methods] The training programmes were conducted in 12 sessions, three 15-min sessions per week. The Nint...

  11. Current enhancement update

    International Nuclear Information System (INIS)

    Net current enhancement to levels in excess of the beam current has been observed in gases at pressures excess of 50 torr. We delineate the regimes where enhancement is observed. The experimental results fall into two very distinct classes; current enhancement at injection where the beam is only slightly displaced and current enhancement clearly associated with the high amplitude hose instability. A careful theoretical and experimental study of the diagnostics revealed no fundamental flaws although there are several complex and unlikely scenarios which could introduce fictitious current enhancement. Theoretical efforts indicate several mechanisms for generating enhancement but none of the theories can account for the detailed observations. 4 references, 4 figures

  12. Parental efficacy, parental monitoring efficacy, and monitoring among Asian-Indian parents of adolescents living in Chennai, India.

    Science.gov (United States)

    Ranganathan, Chitra; Montemayor, Raymond

    2014-12-01

    The purpose of this study was to investigate the relationship between parental efficacy and a new concept entitled parental monitoring efficacy, and to examine the association between parental monitoring efficacy and monitoring. We conducted two studies on two samples of Asian-Indian parents and adolescents living in Chennai, India. In the first study of 241 parents of adolescents in grades, 9-12, we constructed a new measure of parental efficacy that included two factors. The first factor, responding competently to negative adolescent behavior was more strongly predictive of parental monitoring efficacy than the second factor, instilling positive behavior. In the second study of 215 parents and adolescents in grades 10 and 12, parental monitoring efficacy predicted monitoring, especially adolescent disclosure and parental control. The importance of parental control as a monitoring technique among traditional Indian parents was discussed. PMID:25448831

  13. Enhancement of myoblast microencapsulation for gene therapy.

    Science.gov (United States)

    Li, Anna Aihua; Shen, Feng; Zhang, Tao; Cirone, Pasquale; Potter, Murray; Chang, Patricia L

    2006-05-01

    One method of nonviral-based gene therapy is to implant microencapsulated nonautologous cells genetically engineered to secrete the desired gene products. Encapsulating the cells within a biocompatible permselective hydrogel, such as alginate-poly-L-lysine-alginate (APA), protects the foreign cells from the host immune system while allowing diffusion of nutrients and the therapeutic gene products. An important consideration is which kind of cells is the best candidate for long-term implantation. Our previous work has shown that proliferation and differentiation of encapsulated C2C12 myoblasts in vitro are significantly improved by inclusion of basic fibroblast growth factor (bFGF), insulin growth factor II (IGF-II), and collagen within the microcapsules ("enhanced" capsules). However, the effects of such inclusions on the functional status of the microcapsules in vivo are unknown. Here we found that comparing the standard with the enhanced APA microcapsules; there was no difference in the rates of diffusion of recombinant products of different sizes, that is, human factor IX (FIX, 65 kDa), murine IgG (150 kDa), and a lysosomal enzyme, beta-glucuronidase (300 kDa), thus providing a key requirement of such an immunoprotective device. Furthermore, the creatine phosphokinase activity and myosin heavy chain staining (markers for differentiation of the myoblasts) and the cell number per capsule in the enhanced microcapsules indicated a higher degree of differentiation and proliferation when compared to the standard microcapsules, thus demonstrating an improved microenvironment for the encapsulated cells. Efficacy was tested in a melanoma cancer tumor model by treating tumor induced by B16-F0/neu tumor cells in mice with myoblasts secreting angiostatin from either the standard or enhanced APA microcapsules. Mice treated with enhanced APA-microcapsules had an 80% reduction in tumor volume at day 21 compared to a 70% reduction in those treated with standard APA

  14. Improved quality management to enhance the efficacy of the sterile insect technique for lepidopteran pests

    Science.gov (United States)

    Lepidoptera are among the most severe pests of food and fibre crops in the world and are mainly controlled using broad spectrum insecticides. This does not lead to sustainable control and farmers are demanding alternative control tools which are both effective and friendly to the environment. The st...

  15. Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles

    OpenAIRE

    Chen Y; Wan Y; Wang Y; Zhang H.; Jiao Z

    2011-01-01

    Yan Chen1,*, Ying Wan1,*, Yi Wang1, Haijun Zhang2, Zhijun Jiao11Key Laboratory of Medical Immunology and Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang; 2Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China *These authors have contributed equally to this workBackground: Doxorubicin has a broad spectrum of anticancer activity, but its clinical application is limited due to serious ...

  16. Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles

    OpenAIRE

    Mas N; Galiana I; Hurtado S; Mondragón L; Bernardos A; Sancenón F; Marcos MD; Amorós P; Abril-Utrillas N; Martínez-Máñez R; Murguía JR

    2014-01-01

    Núria Mas,1–3 Irene Galiana,3 Silvia Hurtado,† Laura Mondragón,1–3 Andrea Bernardos,1–3 Félix Sancenón,1–3 María D Marcos,1–3 Pedro Amorós,4 Nuria Abril-Utrillas,5 Ramón Martínez-Máñez,1–3 José Ramón Murguía1,3 1Centro de Reconocimiento Molecular y Desarrollo Tecnológico ...

  17. PASylation of Murine Leptin Leads to Extended Plasma Half-Life and Enhanced in Vivo Efficacy.

    Science.gov (United States)

    Morath, Volker; Bolze, Florian; Schlapschy, Martin; Schneider, Sarah; Sedlmayer, Ferdinand; Seyfarth, Katrin; Klingenspor, Martin; Skerra, Arne

    2015-05-01

    Leptin plays a central role in the control of energy homeostasis and appetite and, thus, has attracted attention for therapeutic approaches in spite of its limited pharmacological activity owing to the very short circulation in the body. To improve drug delivery and prolong plasma half-life, we have fused murine leptin with Pro/Ala/Ser (PAS) polypeptides of up to 600 residues, which adopt random coil conformation with expanded hydrodynamic volume in solution and, consequently, retard kidney filtration in a similar manner as polyethylene glycol (PEG). Relative to unmodified leptin, size exclusion chromatography and dynamic light scattering revealed an approximately 21-fold increase in apparent size and a much larger molecular diameter of around 18 nm for PAS(600)-leptin. High receptor-binding activity for all PASylated leptin versions was confirmed in BIAcore measurements and cell-based dual-luciferase assays. Pharmacokinetic studies in mice revealed a much extended plasma half-life after ip injection, from 26 min for the unmodified leptin to 19.6 h for the PAS(600) fusion. In vivo activity was investigated after single ip injection of equimolar doses of each leptin version. Strongly increased and prolonged hypothalamic STAT3 phosphorylation was detected for PAS(600)-leptin. Also, a reduction in daily food intake by up to 60% as well as loss in body weight of >10% lasting for >5 days was observed, whereas unmodified leptin was merely effective for 1 day. Notably, application of a PASylated superactive mouse leptin antagonist (SMLA) led to the opposite effects. Thus, PASylated leptin not only provides a promising reagent to study its physiological role in vivo but also may offer a superior drug candidate for clinical therapy. PMID:25811325

  18. Enhancing the efficacy of electrolytic chlorination for ballast water treatment by adding carbon dioxide.

    Science.gov (United States)

    Cha, Hyung-Gon; Seo, Min-Ho; Lee, Heon-Young; Lee, Ji-Hyun; Lee, Dong-Sup; Shin, Kyoungsoon; Choi, Keun-Hyung

    2015-06-15

    We examined the synergistic effects of CO2 injection on electro-chlorination in disinfection of plankton and bacteria in simulated ballast water. Chlorination was performed at dosages of 4 and 6ppm with and without CO2 injection on electro-chlorination. Testing was performed in both seawater and brackish water quality as defined by IMO G8 guidelines. CO2 injection notably decreased from the control the number of Artemia franciscana, a brine shrimp, surviving during a 5-day post-treatment incubation (1.8 and 2.3 log10 reduction in seawater and brackish water, respectively at 6ppm TRO+CO2) compared with water electro-chlorinated only (1.2 and 1.3 log10 reduction in seawater and brackish water, respectively at 6ppm TRO). The phytoplankton Tetraselmis suecica, was completely disinfected with no live cell found at >4ppm TRO with and without CO2 addition. The effects of CO2 addition on heterotrophic bacterial growth was not different from electro-chlorination only. Total residual oxidant concentration (TRO) more rapidly declined in electro-chlorination of both marine and brackish waters compared to chlorine+CO2 treated waters, with significantly higher amount of TRO being left in waters treated with the CO2 addition. Total concentration of trihalomethanes (THMs) and haloacetic acids (HAAs) measured at day 0 in brackish water test were found to be 2- to 3-fold higher in 6ppm TRO+CO2-treated water than in 6ppm TRO treated water. The addition of CO2 to electro-chlorination may improve the efficiency of this sterilizing treatment of ballast water, yet the increased production of some disinfection byproducts needs further study. PMID:25841887

  19. Determining the efficacy of a nanotechnology media product in enhancing children’s engagement with nanotechnology

    International Nuclear Information System (INIS)

    Public engagement in nanotechnology media products can lead to a greater interest in understanding of nanotechnology. A study was undertaken to determine middle school student engagement in Nanooze, a magazine featuring nanotechnology research that has been developed for a young adult audience. Teachers at 116 Detroit middle schools distributed two issues of the magazine to their students, and surveys were collected from 870 students after reading the magazines. Results suggest that the majority of students liked reading the magazine and learned something about nanotechnology. Engagement in nanotechnology led to understanding of nanotechnology. The Nanooze magazine was an effective medium for engaging middle school students in learning about nanotechnology.

  20. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis

    OpenAIRE

    S.K. Jain; Gill, M. S.; Pawar, H. S.; Sarasija Suresh

    2014-01-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; st...