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Sample records for micellar doxorubicin infused

  1. Pilot study of interaction of radiation therapy with doxorubicin by continuous infusion

    International Nuclear Information System (INIS)

    Rosenthal, C.J.; Rotman, M.

    1988-01-01

    Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas

  2. Concomitant radiation therapy and doxorubicin by continuous Infusion in advanced malignancies - A phase I-II study - evidence of synergistic effect in Soft tissue sarcomas and hepatomas

    International Nuclear Information System (INIS)

    Rosenthal, C.J.; Bhutiani, I.; Rotman, M.

    1986-01-01

    This paper attempts to establish the dose and the duration of administration of doxorubicin infusion having the best therapeutic index and to determine the dose of radiation which in combination with the optimal dose of doxorubicin administered by continuous infusion would have the best therapeutic index. The authors attempt to find the nature and the incidence of side effects of these combined modalities of therapy. The therapeutic effect of the optimal doxorubicin infusion dose in combination with concomitant radiotherapy is assessed in a preliminary study and it was found to have a significant enhancing effect in a few cases of hepatomas and in most of the cases of recurrent and metastatic soft tissue sarcomas

  3. Polymeric micellar pH-sensitive drug delivery system for doxorubicin.

    Science.gov (United States)

    Hrubý, Martin; Konák, Cestmír; Ulbrich, Karel

    2005-03-02

    A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached.

  4. PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when compared to PEGylated liposomal and solution formulations of doxorubicin.

    Science.gov (United States)

    Ryan, Gemma M; Kaminskas, Lisa M; Bulitta, Jürgen B; McIntosh, Michelle P; Owen, David J; Porter, Christopher J H

    2013-11-28

    Improved delivery of chemotherapeutic drugs to the lymphatic system has the potential to augment outcomes for cancer therapy by enhancing activity against lymph node metastases. Uptake of small molecule chemotherapeutics into the lymphatic system, however, is limited. Nano-sized drug carriers have the potential to promote access to the lymphatics, but to this point, this has not been examined in detail. The current study therefore evaluated the lymphatic exposure of doxorubicin after subcutaneous and intravenous administration as a simple solution formulation or when formulated as a doxorubicin loaded PEGylated poly-lysine dendrimer (hydrodynamic diameter 12 nm), a PEGylated liposome (100 nm) and various pluronic micellar formulations (~5 nm) to thoracic lymph duct cannulated rats. Plasma and lymph pharmacokinetics were analysed by compartmental pharmacokinetic modelling in S-ADAPT, and Berkeley Madonna software was used to predict the lymphatic exposure of doxorubicin over an extended period of time. The micelle formulations displayed poor in vivo stability, resulting in doxorubicin profiles that were similar to that observed after administration of the doxorubicin solution formulation. In contrast, the dendrimer formulation significantly increased the recovery of doxorubicin in the thoracic lymph after both intravenous and subcutaneous dosing when compared to the solution or micellar formulation. Dendrimer-doxorubicin also resulted in increases in lymphatic doxorubicin concentrations when compared to the liposome formulation, although liposomal doxorubicin did increase lymphatic transport when compared to the solution formulation. Specifically, the dendrimer formulation increased the recovery of doxorubicin in the lymph up to 30 h post dose by up to 685 fold and 3.7 fold when compared to the solution and liposomal formulations respectively. Using the compartmental model to predict lymphatic exposure to longer time periods suggested that doxorubicin exposure to

  5. Multifunctional doxorubicin/superparamagnetic iron oxide-encapsulated Pluronic F127 micelles used for chemotherapy/magnetic resonance imaging

    Science.gov (United States)

    Lai, Jian-Ren; Chang, Yong-Wei; Yen, Hung-Chi; Yuan, Nai-Yi; Liao, Ming-Yuan; Hsu, Chia-Yen; Tsai, Jai-Lin; Lai, Ping-Shan

    2010-05-01

    Polymeric micelles are frequently used to transport and deliver drugs throughout the body because they protect against degradation. Research on functional polymeric micelles for biomedical applications has generally shown that micelles have beneficial properties, such as specific functionality, enhanced specific tumor targeting, and stabilized nanostructures. The particular aim of this study was to synthesize and characterize multifunctional polymeric micelles for use in controlled drug delivery systems and biomedical imaging. In this study, a theranostic agent, doxorubicin/superparamagnetic iron oxide (SPIO)-encapsulated Pluronic F127 (F127) micelles, was developed for dual chemotherapy/magnetic resonance imaging (MRI) purposes, and the structure and composition of the micellar SPIO were characterized by transmission electron microscopy and magnetic measurements. Our results revealed that the micellar SPIO with a diameter of around 100 nm led to a significant advantage in terms of T2 relaxation as compared with a commercial SPIO contrast agent (Resovist®) without cell toxicity. After doxorubicin encapsulation, a dose-dependent darkening of MR images was observed and HeLa cells were killed by this theranostic micelle. These findings demonstrate that F127 micelles containing chemotherapeutic agents and SPIO could be used as a multifunctional nanocarrier for cancer treatment and imaging.

  6. Enhanced Micellar Catalysis LDRD.

    Energy Technology Data Exchange (ETDEWEB)

    Betty, Rita G.; Tucker, Mark D; Taggart, Gretchen; Kinnan, Mark K.; Glen, Crystal Chanea; Rivera, Danielle; Sanchez, Andres; Alam, Todd Michael

    2012-12-01

    The primary goals of the Enhanced Micellar Catalysis project were to gain an understanding of the micellar environment of DF-200, or similar liquid CBW surfactant-based decontaminants, as well as characterize the aerosolized DF-200 droplet distribution and droplet chemistry under baseline ITW rotary atomization conditions. Micellar characterization of limited surfactant solutions was performed externally through the collection and measurement of Small Angle X-Ray Scattering (SAXS) images and Cryo-Transmission Electron Microscopy (cryo-TEM) images. Micellar characterization was performed externally at the University of Minnesotas Characterization Facility Center, and at the Argonne National Laboratory Advanced Photon Source facility. A micellar diffusion study was conducted internally at Sandia to measure diffusion constants of surfactants over a concentration range, to estimate the effective micelle diameter, to determine the impact of individual components to the micellar environment in solution, and the impact of combined components to surfactant phase behavior. Aerosolized DF-200 sprays were characterized for particle size and distribution and limited chemical composition. Evaporation rates of aerosolized DF-200 sprays were estimated under a set of baseline ITW nozzle test system parameters.

  7. Early transcriptional alteration of histone deacetylases in a murine model of doxorubicin-induced cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Izabela Piotrowska

    Full Text Available Doxorubicin is a potent chemotherapeutic agent that is widely-used to treat a variety of cancers but causes acute and chronic cardiac injury, severely limiting its use. Clinically, the acute side effects of doxorubicin are mostly manageable, whereas the delayed consequences can lead to life-threatening heart failure, even decades after cancer treatment. The cardiotoxicity of doxorubicin is subject to a critical cumulative dose and so dosage limitation is considered to be the best way to reduce these effects. Hence, a number of studies have defined a "safe dose" of the drug, both in animal models and clinical settings, with the aim of avoiding long-term cardiac effects. Here we show that a dose generally considered as safe in a mouse model can induce harmful changes in the myocardium, as early as 2 weeks after infusion. The adverse changes include the development of fibrotic lesions, disarray of cardiomyocytes and a major transcription dysregulation. Importantly, low-dose doxorubicin caused specific changes in the transcriptional profile of several histone deacetylases (HDACs which are epigenetic regulators of cardiac remodelling. This suggests that cardioprotective therapies, aimed at modulating HDACs during doxorubicin treatment, deserve further exploration.

  8. Clinical applications of continuous infusion chemotherapy ahd concomitant radiation therapy

    International Nuclear Information System (INIS)

    Rosenthal, C.J.; Rotman, M.

    1986-01-01

    This book presents information on the following topics: theoretical basis and clinical applications of 5-FU as a radiosensitizer; treatment of hepatic metastases from gastro intestingal primaries with split course radiation therapy; combined modality therapy with 5-FU, Mitomycin-C and radiation therapy for sqamous cell cancers; treatment of bladder carcinoma with concomitant infusion chemotherapy and irradiation; a treatment of invasiv bladder cancer by the XRT/5FU protocol; concomitant radiation therapy and doxorubicin by continuous infusion in advanced malignancies; cis platin by continuous infusion with concurrent radiation therapy in malignant tumors; combination of radiation with concomitant continuous adriamycin infusion in a patient with partially excised pleomorphic soft tissue sarcoma of the lower extremeity; treatment of recurrent carcinoma of the paranasal sinuses using concomitant infusion cis-platinum and radiation therapy; hepatic artery infusion for hepatic metastases in combination with hepatic resection and hepatic radiation; study of simultaneous radiation therapy, continuous infusion, 5FU and bolus mitomycin-C; cancer of the esophagus; continuous infusion VP-16, bolus cis-platinum and simultaneous radiation therapy as salvage therapy in small cell bronchogenic carcinoma; and concomitant radiation, mitomycin-C and 5-FU infusion in gastro intestinal cancer

  9. PH-triggered micellar membrane for controlled release microchips

    KAUST Repository

    Yang, Xiaoqiang

    2011-01-01

    A pH-responsive membrane based on polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer was developed on a model glass microchip as a promising controlled polymer delivery system. The PS-b-P4VP copolymer assembles into spherical and/or worm-like micelles with styrene block cores and pyridine coronas in selective solvents. The self-assembled worm-like morphology exhibited pH-responsive behaviour due to the protonation of the P4VP block at low pH and it\\'s deprotonation at high pH and thus constituting a switchable "off/on" system. Doxorubicin (Dox) was used as cargo to test the PS-b-P4VP membrane. Luminescence experiments indicated that the membrane was able to store Dox molecules within its micellar structure at neutral pH and then release them as soon as the pH was raised to 8.0. The performance of the cast membrane was predictable and most importantly reproducible. The physiochemical and biological properties were also investigated carefully in terms of morphology, cell viability and cell uptake. This journal is © The Royal Society of Chemistry.

  10. Theoretical, clinical and pharmacokinetic aspects of cancer chemotherapy administered by continuous infusion

    International Nuclear Information System (INIS)

    Sikic, B.I.

    1986-01-01

    This chapter reviews some of the theoretical and empirical aspects of the administration of anti-cancer drugs by continuous intravenous infusion in conjunction with radiation therapy. The variables contributing to schedule dependence of anti-cancer drugs are discussed. A table shows the improved therapeutic index of Bleomycin by continuous infusion in mice. The use of Cytarabine, a pyrimidine anti-metabolite which kills cells during S-phase or DNA synthesis, is examined. Fluorouracil and Doxorubicin are examined and several other drugs including vincristine, vinblastine, etoposide, and cisplatin are discussed

  11. Pressure-induced melting of micellar crystal

    DEFF Research Database (Denmark)

    Mortensen, K.; Schwahn, D.; Janssen, S.

    1993-01-01

    that pressure improves the solvent quality of water, thus resulting in decomposition of the micelles and consequent melting of the micellar crystal. The combined pressure and temperature dependence reveals that in spite of the apparent increase of order on the 100 angstrom length scale upon increasing......Aqueous solutions of triblock copolymers of poly(ethylene oxide) and poly(propylene oxide) aggregate at elevated temperatures into micelles which for polymer concentrations greater-than-or-equal-to 20% make a hard sphere crystallization to a cubic micellar crystal. Structural studies show...... temperature (decreasing pressure) the overall entropy increases through the inverted micellar crystallization characteristic....

  12. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    International Nuclear Information System (INIS)

    Kamendi, Harriet; Zhou, Ying; Crosby, Meredith; Keirstead, Natalie; Snow, Debra; Bentley, Patricia; Patel, Nilaben; Barthlow, Herbert; Luo, Wenli; Dragan, Yvonne; Bialecki, Russell

    2015-01-01

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  13. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Zhou, Ying, E-mail: yingzhou526@gmail.com [Oncology Innovative Medicines and Early Development, AstraZeneca, Waltham, MA 02451 (United States); Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Keirstead, Natalie, E-mail: Nkeirstead@alnylam.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Snow, Debra, E-mail: Debra.snow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bentley, Patricia, E-mail: patricia.bentley@abbvie.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Patel, Nilaben, E-mail: patelnilaben@yahoo.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Barthlow, Herbert, E-mail: Herbert.barthlow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Luo, Wenli, E-mail: Wenli.luo@astrazeneca.com [Discovery Sciences, Innovative Medicines, AstraZeneca, Waltham, MA 02451 (United States); Dragan, Yvonne, E-mail: Yvonne.P.Dragan@takeda.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States)

    2015-12-15

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  14. Recirculation and reutilization of micellar bile lecithin.

    Science.gov (United States)

    Robins, S J

    1975-09-01

    Bile lecithins, solubilized in micellar bile salt and radiolabeled in the 1-acyl fatty acid, phosphorus, and choline positions, were infused in the small bowel of fasted rats. Absorption of each label was virtually complete after 24 h. However, these lecithins were extensively hydrolyzed in the bowel lumen as well as after absorption, and neither the fatty acid nor phosphorus was significantly retained in the enterohepatic circulation or reutilized for biliary lecithin synthesis. In contrast, while choline was also dissociated from absorbed lecithin, choline was instead retained in the liver, reincorporated into newly synthesized hepatic lecithin, and sercreted in biliary lecithin in 10-fold greater amounts than either the fatty acid or phosphorus. However, the extent of choline incorporation into bile lecithin was limited and was not further increased when free choline was directly injected into the portal vein. The data therefore suggest that although only choline of absorbed lecithin is retained in the enterohepatic circulation and preserved for new biliary lecithin synthesis, exogenous choline utilization is regulated by the size of the available hepatic pool.

  15. Biological activity and photostability of biflorin micellar nanostructures.

    Science.gov (United States)

    Santana, Edson R B; Ferreira-Neto, João P; Yara, Ricardo; Sena, Kêsia X F R; Fontes, Adriana; Lima, Cláudia S A

    2015-05-13

    Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR) and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9%) and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS). The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures' photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.

  16. Biological Activity and Photostability of Biflorin Micellar Nanostructures

    Directory of Open Access Journals (Sweden)

    Edson R. B. Santana

    2015-05-01

    Full Text Available Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9% and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS. The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures’ photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.

  17. Profluorescent PPV-Based Micellar System as a Versatile Probe for Bioimaging and Drug Delivery.

    Science.gov (United States)

    Zaquen, Neomy; Lu, Hongxu; Chang, Teddy; Mamdooh, Russel; Lutsen, Laurence; Vanderzande, Dirk; Stenzel, Martina; Junkers, Thomas

    2016-12-12

    Although micelles are commonly used for drug delivery purposes, their long-term fate is often unknown due to photobleaching of the fluorescent labels or the use of toxic materials. Here, we present a metal-free, nontoxic, nonbleaching, fluorescent micelle that can address these shortcomings. A simple, yet versatile, profluorescent micellar system, built from amphiphilic poly(p-phenylenevinylene) (PPV) block copolymers, for use in drug delivery applications is introduced. Polymer micelles made from PPV show excellent stability for up to 1 year and are successfully loaded with anticancer drugs (curcumin or doxorubicin) without requiring introduction of physical or chemical cross-links. The micelles are taken up efficiently by the cells, which triggers disassembly, releasing the encapsulated material. Disassembly of the micelles and drug release is conveniently monitored as fluorescence of the single polymer chains appear, which enables not only to monitor the release of the payload, but in principle also the fate of the polymer over longer periods of time.

  18. Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

    Science.gov (United States)

    Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

    2012-05-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

  19. Effect of doxorubicin and daunorubicin on the activity of acetylcholinesterase in acute lymphoblastic leukamia

    International Nuclear Information System (INIS)

    Din, I.U.; Ali, A.

    2011-01-01

    Background: Our study was based on the alteration in the Michaelis Mentin parameters Apparent Michaelis Constant (aKm) and Apparent Maximum Velocity (aVm), which reflects activity of actyl cholinesterase (AChE). This activity decreases in Acute Lymphoblastic Leukaemia (ALL). This decrease in aKm and aVm values shows bad prognosis. Similarly the anticancer drugs like Daunorubicin and Doxorubicin further decreases the aKm and aVm values which worsen the prognosis. The objective of this study was to determine and compare the extent of inhibition of Acetylcholine Esterase by Daunorubicin and Doxorubicin in ALL. Methods: Study of 100 patients including both male and female children who's age ranged from 4 to 8 years and were advised doxorubicin and daunorubicin separately were tested by Ellman's method using acetylcholine iodide as substrate and 5,5-dithiobis 2-nitrobenzine as a colour reagent regardless of dose regimen i.e. (once in 3 week, small dose per week or a continuous infusion for 72 to 96 hours. Results: In this study the Michaelis Mentin parameters Apparent Michaelis Constant (aKm) and Apparent Maximum Velocity (aVm) of the enzyme were estimated both in normal individuals and in the patients and also during treatment with daunorubicin and doxorubicin. The value of Michaelis Mentin parameters, aKm, aVm and percentage activity of the enzyme in normal individual are 23, 70, and 100 respectively. The values of aKm, aVm and percentage activity of the enzyme were also estimated in the patients before and after treatment. The values of aKm and aVm in patients of acute lymphoblastic leukaemia and percentage activity of enzyme is decreased. After the treatment with daunorubicin and doxorubicin the values and activity is further decreased. Conclusion: We conclude that the drugs under study both decrease the enzyme activity but daunorubicin inhibits the enzyme more than doxorubicin. (author)

  20. Two-phase aqueous micellar systems: an alternative method for protein purification

    Directory of Open Access Journals (Sweden)

    Rangel-Yagui C. O.

    2004-01-01

    Full Text Available Two-phase aqueous micellar systems can be exploited in separation science for the extraction/purification of desired biomolecules. This article reviews recent experimental and theoretical work by Blankschtein and co-workers on the use of two-phase aqueous micellar systems for the separation of hydrophilic proteins. The experimental partitioning behavior of the enzyme glucose-6-phosphate dehydrogenase (G6PD in two-phase aqueous micellar systems is also reviewed and new results are presented. Specifically, we discuss very recent work on the purification of G6PD using: i a two-phase aqueous micellar system composed of the nonionic surfactant n-decyl tetra(ethylene oxide (C10E4, and (ii a two-phase aqueous mixed micellar system composed of C10E4 and the cationic surfactant decyltrimethylammonium bromide (C10TAB. Our results indicate that the two-phase aqueous mixed (C10E4/C10TAB micellar system can improve significantly the partitioning behavior of G6PD relative to that observed in the two-phase aqueous C10E4 micellar system.

  1. Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ming-Chun Ma

    2014-01-01

    Full Text Available Advanced hepatocellular carcinoma (HCC remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m2 and cisplatin (50 mg/m2 infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I and those who received several cycles (group II. The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P<0.0001. The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P<0.0001. The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT.

  2. Catalysis in micellar and macromoleular systems

    CERN Document Server

    Fendler, Janos

    1975-01-01

    Catalysis in Micellar and Macromolecular Systems provides a comprehensive monograph on the catalyses elicited by aqueous and nonaqueous micelles, synthetic and naturally occurring polymers, and phase-transfer catalysts. It delineates the principles involved in designing appropriate catalytic systems throughout. Additionally, an attempt has been made to tabulate the available data exhaustively. The book discusses the preparation and purification of surfactants; the physical and chemical properties of surfactants and micelles; solubilization in aqueous micellar systems; and the principles of

  3. Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

    Science.gov (United States)

    Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

    2012-01-01

    Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

  4. New approach in synthesis, characterization and release study of pH-sensitive polymeric micelles, based on PLA-Lys-b-PEGm, conjugated with doxorubicin

    International Nuclear Information System (INIS)

    Efthimiadou, E. K.; Tapeinos, C.; Bilalis, P.; Kordas, G.

    2011-01-01

    Amphiphilic block copolymers are well established as building blocks for the preparation of micellar drug carriers. The functional polymer micelles possess several advantages, such as high drug efficiency, targeted delivery, and minimized cytotoxicity. The synthesis of block copolymers using nano-structured templates has emerged as a useful and versatile approach for preparing drug carriers. Here, we report the synthesis of a smart polymeric compound of a diblock PLA-Lys-b-PEG copolymer containing doxorubicin. We have synthesized functionalized diblock copolymers, with lysinol, poly(lactide) and monomethoxy poly(ethylene glycol) via thermal ring-opening polymerization and a subsequent six-step substitution reaction. A variety of spectroscopic methods were employed here to verify the product of our synthesis. 1 H-Nuclear magnetic resonance and Fourier transform infrared studies validated the expected synthesis of copolymers. Doxorubicin is chemically loaded into micelles, and the ex vitro release can be evaluated either in weak acidic or in SBF solution by UV–vis spectroscopy. Dynamic light scattering, thermo gravimetric analysis, and size exclusion chromatography have also been used.

  5. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial.

    Science.gov (United States)

    Tap, William D; Papai, Zsuzsanna; Van Tine, Brian A; Attia, Steven; Ganjoo, Kristen N; Jones, Robin L; Schuetze, Scott; Reed, Damon; Chawla, Sant P; Riedel, Richard F; Krarup-Hansen, Anders; Toulmonde, Maud; Ray-Coquard, Isabelle; Hohenberger, Peter; Grignani, Giovanni; Cranmer, Lee D; Okuno, Scott; Agulnik, Mark; Read, William; Ryan, Christopher W; Alcindor, Thierry; Del Muro, Xavier F Garcia; Budd, G Thomas; Tawbi, Hussein; Pearce, Tillman; Kroll, Stew; Reinke, Denise K; Schöffski, Patrick

    2017-08-01

    Evofosfamide is a hypoxia-activated prodrug of bromo-isophosphoramide mustard. We aimed to assess the benefit of adding evofosfamide to doxorubicin as first-line therapy for advanced soft-tissue sarcomas. We did this international, open-label, randomised, phase 3, multicentre trial (TH CR-406/SARC021) at 81 academic or community investigational sites in 13 countries. Eligible patients were aged 15 years or older with a diagnosis of an advanced unresectable or metastatic soft-tissue sarcoma, of intermediate or high grade, for which no standard curative therapy was available, an Eastern Cooperative Oncology Group performance status of 0-1, and measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (1:1) to receive doxorubicin alone (75 mg/m 2 via bolus injection administered over 5-20 min or continuous intravenous infusion for 6-96 h on day 1 of every 21-day cycle for up to six cycles) or doxorubicin (given via the same dose procedure) plus evofosfamide (300 mg/m 2 intravenously for 30-60 min on days 1 and 8 of every 21-day cycle for up to six cycles). After six cycles of treatment, patients in the single-drug doxorubicin group were followed up expectantly whereas patients with stable or responsive disease in the combination group were allowed to continue with evofosfamide monotherapy until documented disease progression. A web-based central randomisation with block sizes of two and four was stratified by extent of disease, doxorubicin administration method, and previous systemic therapy. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival, analysed in the intention-to-treat population. Safety analyses were done in all patients who received any amount of study drug. This study was registered with ClinicalTrials.gov, number NCT01440088. Between Sept 26, 2011, and Jan 22, 2014, 640 patients were enrolled and randomly assigned to a treatment group (317 to

  6. Compound list: doxorubicin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available doxorubicin DOX 00149 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/...in_vitro/doxorubicin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_...vitro/doxorubicin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/...Liver/Single/doxorubicin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/...archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/doxorubicin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bios

  7. Role of aldo-keto reductases and other doxorubicin pharmacokinetic genes in doxorubicin resistance, DNA binding, and subcellular localization

    International Nuclear Information System (INIS)

    Heibein, Allan D; Guo, Baoqing; Sprowl, Jason A; MacLean, David A; Parissenti, Amadeo M

    2012-01-01

    Since proteins involved in chemotherapy drug pharmacokinetics and pharmacodynamics have a strong impact on the uptake, metabolism, and efflux of such drugs, they likely play critical roles in resistance to chemotherapy drugs in cancer patients. To investigate this hypothesis, we conducted a whole genome microarray study to identify difference in the expression of genes between isogenic doxorubicin-sensitive and doxorubicin-resistant MCF-7 breast tumour cells. We then assessed the degree of over-representation of doxorubicin pharmacokinetic and pharmacodynamic genes in the dataset of doxorubicin resistance genes. Of 27,958 Entrez genes on the array, 7.4 per cent or 2,063 genes were differentially expressed by ≥ 2-fold between wildtype and doxorubicin-resistant cells. The false discovery rate was set at 0.01 and the minimum p value for significance for any gene within the “hit list” was 0.01. Seventeen and 43 per cent of doxorubicin pharmacokinetic genes were over-represented in the hit list, depending upon whether the gene name was identical or within the same gene family, respectively. The most over-represented genes were within the 1C and 1B families of aldo-keto reductases (AKRs), which convert doxorubicin to doxorubicinol. Other genes convert doxorubicin to other metabolites or affect the influx, efflux, or cytotoxicity of the drug. In further support of the role of AKRs in doxorubicin resistance, we observed that, in comparison to doxorubicin, doxorubincol exhibited dramatically reduced cytotoxicity, reduced DNA-binding activity, and strong localization to extra nuclear lysosomes. Pharmacologic inhibition of the above AKRs in doxorubicin-resistant cells increased cellular doxorubicin levels, restored doxorubicin cytotoxicity and re-established doxorubicin localization to the nucleus. The properties of doxorubicinol were unaffected. These findings demonstrate the utility of using curated pharmacokinetic and pharmacodynamic knowledge bases to identify

  8. Principles of Micellar Electrokinetic Capillary Chromatography Applied in Pharmaceutical Analysis

    Directory of Open Access Journals (Sweden)

    Árpád Gyéresi

    2013-02-01

    Full Text Available Since its introduction capillary electrophoresis has shown great potential in areas where electrophoretic techniques have rarely been used before, including here the analysis of pharmaceutical substances. The large majority of pharmaceutical substances are neutral from electrophoretic point of view, consequently separations by the classic capillary zone electrophoresis; where separation is based on the differences between the own electrophoretic mobilities of the analytes; are hard to achieve. Micellar electrokinetic capillary chromatography, a hybrid method that combines chromatographic and electrophoretic separation principles, extends the applicability of capillary electrophoretic methods to neutral analytes. In micellar electrokinetic capillary chromatography, surfactants are added to the buffer solution in concentration above their critical micellar concentrations, consequently micelles are formed; micelles that undergo electrophoretic migration like any other charged particle. The separation is based on the differential partitioning of an analyte between the two-phase system: the mobile aqueous phase and micellar pseudostationary phase. The present paper aims to summarize the basic aspects regarding separation principles and practical applications of micellar electrokinetic capillary chromatography, with particular attention to those relevant in pharmaceutical analysis.

  9. Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy.

    Science.gov (United States)

    Leal, A D; Kadakia, K C; Looker, S; Hilger, C; Sorgatz, K; Anderson, K; Jacobson, A; Grendahl, D; Seisler, D; Hobday, T; Loprinzi, Charles L

    2014-05-01

    The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

  10. Doxorubicin impairs the insulin-like growth factor-1 system and causes insulin-like growth factor-1 resistance in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Patrizia Fabbi

    Full Text Available Insulin-like growth factor-1 (IGF-1 promotes the survival of cardiomyocytes by activating type 1 IGF receptor (IGF-1R. Within the myocardium, IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3, which sequesters IGF-1 away from IGF-1R. Since cardiomyocyte apoptosis is implicated in anthracycline cardiotoxicity, we investigated the effects of the anthracycline, doxorubicin, on the IGF-1 system in H9c2 cardiomyocytes.Besides inducing apoptosis, concentrations of doxorubicin comparable to those observed in patients after bolus infusion (0.1-1 µM caused a progressive decrease in IGF-1R and increase in IGFBP-3 expression. Exogenous IGF-1 was capable to rescue cardiomyocytes from apoptosis triggered by 0.1 and 0.5 µM, but not 1 µM doxorubicin. The loss of response to IGF-1 was paralleled by a significant reduction in IGF-1 availability and signaling, as assessed by free hormone levels in conditioned media and Akt phosphorylation in cell lysates, respectively. Doxorubicin also dose-dependently induced p53, which is known to repress the transcription of IGF1R and induce that of IGFBP3. Pre-treatment with the p53 inhibitor, pifithrin-α, prevented apoptosis and the changes in IGF-1R and IGFBP-3 elicited by doxorubicin. The decrease in IGF-1R and increase in IGFBP-3, as well as apoptosis, were also antagonized by pre-treatment with the antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol.Doxorubicin down-regulates IGF-1R and up-regulates IGFBP-3 via p53 and oxidative stress in H9c2 cells. This leads to resistance to IGF-1 that may contribute to doxorubicin-initiated apoptosis. Further studies are needed to confirm these findings in human cardiomyocytes and explore the possibility of manipulating the IGF-1 axis to protect against anthracycline cardiotoxicity.

  11. Doxorubicin-induced second degree and complete atrioventricular block.

    Science.gov (United States)

    Kilickap, Saadettin; Akgul, Ebru; Aksoy, Sercan; Aytemir, Kudret; Barista, Ibrahim

    2005-05-01

    Doxorubicin is one of the most effective chemotherapeutic agents used in the treatment of malignancies. Cardiotoxicity is the most important dose-limiting toxicity of doxorubicin. Although cardiomyopathy is the most well known side effect of doxorubicin, it usually occurs many years after the treatment and relates to cumulative doxorubicin dosage. Another form of doxorubicin cardiotoxicity is arrhythmia which may occur at any time and after any dosage. However, doxorubicin-induced arrhythmia is rarely a life-threatening side effect. In this report, we present a case in which there were doxorubicin-induced life-threatening arrhythmias.

  12. Octane-Assisted Reverse Micellar Dyeing of Cotton with Reactive Dyes

    Directory of Open Access Journals (Sweden)

    Alan Yiu-lun Tang

    2017-12-01

    Full Text Available In this study, we investigated the computer colour matching (CCM of cotton fabrics dyed with reactive dye using the octane-assisted reverse micellar approach. The aim of this study is to evaluate the colour quality and compare the accuracy between CCM forecasting and simulated dyeing produced by conventional water-based dyeing and octane-assisted reverse micellar dyeing. First, the calibration of dyeing databases for both dyeing methods was established. Standard samples were dyed with known dye concentrations. Computer colour matching was conducted by using the colour difference formula of International Commission on Illumination (CIE L*a*b*. Experimental results revealed that the predicted concentrations were nearly the same as the expected known concentrations for both dyeing methods. This indicates that octane-assisted reverse micellar dyeing system can achieve colour matching as good as the conventional water-based dyeing system. In addition, when comparing the colour produced by the conventional water-based dyeing system and the octane-assisted reverse micellar dyeing system, the colour difference (ΔE is ≤1, which indicates that the reverse micellar dyeing system could be applied for industrial dyeing with CCM.

  13. High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas--rationale for combination with radiotherapy

    International Nuclear Information System (INIS)

    Koukourakis, M.I.; Koukouraki, S.; Giatromanolaki, A.; Kakolyris, S.; Georgoulias, V.; Velidaki, A.; Archimandritis, S.; Karkavitsas, N.N.

    2000-01-01

    Sarcomas are radioresistant tumors, the only curative therapy being radical surgical resection. Stealth liposomal doxorubicin (Caelyx) is a novel drug formulation that allows prolonged circulation and high intratumoral concentration. This study investigates the concurrent use of radiotherapy with Caelyx in a cohort of 7 patients with locally advanced or recurrent sarcoma. Radiotherapy was given as a standard fractionation regimen to a total dose of 70 Gy. Caelyx was given as a 30-min infusion at a dose of 25 mg/m 2 every 2 weeks. Scintigraphic imaging with Caelyx- 99m Tc-DTPA showed an increased (2.8 +/- 0.9 times higher) intratumoral drug accumulation compared to the surrounding healthy tissue. The regimen was well tolerated without any severe hematological or systemic toxicity. 'In field' radiation toxicity was not increased. Complete response was observed in 4/7 cases. It is concluded that combined chemo-radiotherapy with stealth liposomal doxorubicin for locally advanced sarcomas is feasible and promising, the benefit expected from the unique ability of the stealth liposomes to accumulate selectively in the tumoral tissue

  14. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma

    DEFF Research Database (Denmark)

    Judson, Ian; Verweij, Jaap; Gelderblom, Hans

    2014-01-01

    BACKGROUND: Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used...

  15. Pyrene absorption can be a convenient method for probing critical micellar concentration (cmc) and indexing micellar polarity.

    Science.gov (United States)

    Basu Ray, Gargi; Chakraborty, Indranil; Moulik, Satya P

    2006-02-01

    The critical micellar concentration (cmc) of both ionic and non-ionic surfactants can be conveniently determined from the measurements of UV absorption of pyrene in surfactant solution. The results on a number of surfactants have agreed with that realized from pyrene fluorescence measurements as well as that obtained following conductometric, tensiometric and calorimetric methods. The absorbance vs [surfactant] profiles for all the major UV spectral peaks of pyrene have been found to be sigmoidal in nature which were analyzed according to Sigmoidal-Boltzmann equation (SBE) to evaluate the cmcs of the studied surfactants. The difference between the initial and the final asymptotes (a(i) and a(f), respectively) of the sigmoidal profile, Delta a = (a(f)-a(i)) and the slope of the sigmoid, S(sig) have been observed to depend on the type of the surfactant. The Delta a has shown a linear correlation with the ratio of the fluorescence intensities of the first and the third vibronic peaks, I1/I3 of pyrene which is considered as a measure of the environmental polarity (herein micellar interior) of the probe (pyrene). Thus, Delta a values have the prospect for use as another index for the estimation of polarity of micellar interior.

  16. Effects of quercetin on kidney injury induced by doxorubicin.

    Science.gov (United States)

    Yagmurca, M; Yasar, Z; Bas, O

    2015-01-01

    The anthracycline antitumor drug doxorubicine causes severe nephrotoxicity in a variety of experimental animals and may be nephrotoxic to humans. The aim of present study was to determine the protective effects of quercetin against doxorubicin-induced kidney injury with light microscopy. Forty male Wistar albino rats were divided into four groups: control, doxorubicin, doxorubicin+quercetin and quercetin. A single dose of 20 mg/kg/ i.p. doxorubicin was used to induce injury. Quercetin was administrated orally against doxorubicin toxicity. The kidneys were examined under light microscopy after H-E (hematoxylin-eosin) staining and the changes were scored. Significant tissue injury was observed in doxorubicin-administered group. Among these injuries, renal tubular dilatation, tubular vacuolar changes, glomerular vacuolization, decrease in bowman space, bowman capsule thickening, and interstitial infiltration were evident. However, the injury induced by doxorubicin was attenuated with quercetin administration. Quercetin decreased doxorubicin-induced kidney damage (Tab. 1, Fig. 4, Ref. 27).

  17. Micellar Catalysis of Diels-Alder Reactions : Substrate Positioning in the Micelle

    NARCIS (Netherlands)

    Rispens, Theo; Engberts, Jan B.F.N.

    2002-01-01

    We have studied the kinetics of the Diels-Alder reactions of cyclopentadiene, sorbyl alcohol, and sorbyltrimethylammonium bromide with a series of N-substituted maleimides in micellar media. Micellar rate constants have been determined and were found to be 20-40 times lower than the respective

  18. Study of the Reaction 2-(p-Nitrophenylethyl Bromide + OH− in Dimeric Micellar Solutions

    Directory of Open Access Journals (Sweden)

    María Luisa Moyá

    2011-11-01

    Full Text Available The dehydrobromination reaction 2-(p-nitrophenylethyl bromide + OH− was investigated in several alkanediyl-a-w-bis(dodecyldimethylammonium bromide, 12-s-12,2Br− (with s = 2, 3, 4, 5, 6, 8, 10, 12 micellar solutions, in the presence of NaOH 5 × 10−3 M. The kinetic data were quantitatively rationalized within the whole surfactant concentration range by using an equation based on the pseudophase ion-exchange model and taking the variations in the micellar ionization degree caused by the morphological transitions into account. The agreement between the theoretical and the experimental data was good in all the dimeric micellar media studied, except for the 12-2-12,2Br− micellar solutions. In this case, the strong tendency to micellar growth shown by the 12-2-12,2Br− micelles could be responsible for the lack of accordance. Results showed that the dimeric micelles accelerate the reaction more than two orders of magnitude as compared to water.

  19. Phase separation in living micellar networks

    Science.gov (United States)

    Cristobal, G.; Rouch, J.; Curély, J.; Panizza, P.

    We present a lattice model based on two n→0 spin vectors, capable of treating the thermodynamics of living networks in micellar solutions at any surfactant concentration. We establish an isomorphism between the coupling constants in the two spin vector Hamiltonian and the surfactant energies involved in the micellar situation. Solving this Hamiltonian in the mean-field approximation allows one to calculate osmotic pressure, aggregation number, free end and cross-link densities at any surfactant concentration. We derive a phase diagram, including changes in topology such as the transition between spheres and rods and between saturated and unsaturated networks. A phase separation can be found between a saturated network and a dilute solution composed of long flexible micelles or a saturated network and a solution of spherical micelles.

  20. Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats

    International Nuclear Information System (INIS)

    Kalender, Yusuf; Yel, Mustafa; Kalender, Suna

    2005-01-01

    Doxorubicin (DXR) is an anthracycline antibiotic, broady used in tumor therapy. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of doxorubicin. Vitamin E (200 IU/kg/week), catechin (200 mg/kg/week), doxorubicin (5 mg/kg/week), doxorubicin + vitamin E (200 IU/kg/week), doxorubicin + catechin (200 mg/kg/week) combinations were given to rats weighing 210-230 g (n = 6/group). Changes in major enzymes participating in free radical metabolism superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSHPx), catalase (CAT) and malondialdehyde (MDA) were evaluated in the livers of all animals. Superoxide dismutase and catalase activity increased in the doxorubicin-treated group compared to control (P 0.05). Electron microscopic studies supported biochemical findings. We conclude that vitamin E and catechin significantly reduce doxorubicin-induced hepatotoxicity in rats

  1. Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy and side effect attenuation

    International Nuclear Information System (INIS)

    Zhu, Zhi-feng; Yao, Zhi; Chen, Li-juan; Lu, Rong; Jia, Jing; Liang, Yu; Xu, Qiong; Zhou, Chun-lei; Wang, Li; Wang, Song

    2008-01-01

    Tripeptide tyroserleutide (YSL) is a novel small molecule anti-tumor polypeptide that has been shown to inhibit the growth of human liver cancer cells. In this study, we investigated the effects of YSL plus doxorubicin on the growth of human hepatocellular carcinoma BEL-7402 cells that had been transplanted into nude mice. Nude mice bearing human hepatocellular carcinoma BEL-7402 tumors were treated with successive intraperitoneal injections of saline; low-, mid-, or high-dose doxorubicin; or low-, mid-, or high-dose doxorubicin plus YSL. Effects on the weight and volume of the tumors were evaluated. Co-administration of YSL and high-dose doxorubicin (6 mg/kg every other day) prolonged the survival time of tumor-bearing mice as compared to high-dose doxorubicin alone. As well, the anti-tumor effects of mid- and low-dose doxorubicin (2 and 0.7 mg/kg every other day, respectively) were enhanced when supplemented with YSL; the tumor growth inhibition rates for YSL plus doxorubicin were greater than the inhibition rates for the same dosages of doxorubicin alone. The combination of YSL and doxorubicin decreased chemotherapy-associated weight loss, leukocyte depression, and heart, liver, and kidney damage as compared to doxorubicin alone. The combination of YSL plus doxorubicin enhances the anti-tumor effect and reduces the side effects associated with doxorubicin chemotherapy

  2. 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 To determine the effect of different drug-loaded nanocarriers (micelles and liposomes on delivery and treatment efficacy for radiofrequency ablation (RFA combined with nanodrugs.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.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.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 accumulation over time and reduced tumor growth. Accordingly

  3. Au/CdS Hybrid Nanoparticles in Block Copolymer Micellar Shells.

    Science.gov (United States)

    Koh, Haeng-Deog; Changez, Mohammad; Lee, Jae-Suk

    2010-10-18

    A polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) micellar structure with a P2VP core containing 5 nm CdS nanoparticles (NPs) and a PS shell formed in toluene that is a good solvent for PS block undergoes the core-shell inversion by excess addition of methanol that is a good solvent for P2VP block. It leads to the formation of micellar shell-embedded CdS NPs in the methanol major phase. The spontaneous crystalline growth of Au NPs on the CdS surfaces positioned at micellar shells without a further reduction process is newly demonstrated. The nanostructure of Au/CdS/PS-b-P2VP hybrid NPs is confirmed by transmission electron microscopy, energy-dispersive X-ray, and UV-Vis absorption. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

    Directory of Open Access Journals (Sweden)

    Zbynek Heger

    2013-10-01

    Full Text Available Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine. An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05. This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.

  5. Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

    Science.gov (United States)

    Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

    2017-02-05

    The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Impact of thermooxidation of phytosteryl and phytostanyl fatty acid esters on cholesterol micellarization in vitro.

    Science.gov (United States)

    Scholz, Birgit; Weiherer, Renate; Engel, Karl-Heinz

    2017-09-01

    The effects of thermooxidation of a phytosteryl/-stanyl and a phytostanyl fatty acid ester mixture on cholesterol micellarization were investigated using an in vitro digestion model simulating enzymatic hydrolysis by cholesterol esterase and subsequent competition of the liberated phytosterols/-stanols with cholesterol for incorporation into mixed micelles. As a first step, relationships between different doses of the ester mixtures and the resulting micellarized cholesterol were established. Subsequent subjection of the thermooxidized ester mixtures to the in vitro digestion model resulted in three principal observations: (i) thermal treatment of the ester mixtures led to substantial decreases of the intact esters, (ii) in vitro digestion of cholesterol in the presence of the thermooxidized ester mixtures resulted in significant increases of cholesterol micellarization, and (iii) the extents of the observed effects on cholesterol micellarization were strongly associated to the remaining contents of intact esters. The loss of efficacy to inhibit cholesterol micellarization due to thermally induced losses of intact esters corresponded to a loss of efficacy that would have been induced by an actual removal of these amounts of esters prior to the in vitro digestion. The obtained results suggest that in particular oxidative modifications of the fatty acid moieties might be responsible for the observed increases of cholesterol micellarization. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Doxorubicin Blocks Cardiomyocyte Autophagic Flux by Inhibiting Lysosome Acidification.

    Science.gov (United States)

    Li, Dan L; Wang, Zhao V; Ding, Guanqiao; Tan, Wei; Luo, Xiang; Criollo, Alfredo; Xie, Min; Jiang, Nan; May, Herman; Kyrychenko, Viktoriia; Schneider, Jay W; Gillette, Thomas G; Hill, Joseph A

    2016-04-26

    The clinical use of doxorubicin is limited by cardiotoxicity. Histopathological changes include interstitial myocardial fibrosis and the appearance of vacuolated cardiomyocytes. Whereas dysregulation of autophagy in the myocardium has been implicated in a variety of cardiovascular diseases, the role of autophagy in doxorubicin cardiomyopathy remains poorly defined. Most models of doxorubicin cardiotoxicity involve intraperitoneal injection of high-dose drug, which elicits lethargy, anorexia, weight loss, and peritoneal fibrosis, all of which confound the interpretation of autophagy. Given this, we first established a model that provokes modest and progressive cardiotoxicity without constitutional symptoms, reminiscent of the effects seen in patients. We report that doxorubicin blocks cardiomyocyte autophagic flux in vivo and in cardiomyocytes in culture. This block was accompanied by robust accumulation of undegraded autolysosomes. We go on to localize the site of block as a defect in lysosome acidification. To test the functional relevance of doxorubicin-triggered autolysosome accumulation, we studied animals with diminished autophagic activity resulting from haploinsufficiency for Beclin 1. Beclin 1(+/-) mice exposed to doxorubicin were protected in terms of structural and functional changes within the myocardium. Conversely, animals overexpressing Beclin 1 manifested an amplified cardiotoxic response. Doxorubicin blocks autophagic flux in cardiomyocytes by impairing lysosome acidification and lysosomal function. Reducing autophagy initiation protects against doxorubicin cardiotoxicity. © 2016 American Heart Association, Inc.

  8. Renal damage induced by dosorubicin-lipiodol emulsion infused into rabbit renal artery : comparison with CT and histologic findings

    International Nuclear Information System (INIS)

    Kim, Jin Gyoo; Moon, Tae Young; Lee, Suck Hong; Kim, Byung Soo; Choi, Sang Yul; Park, Choong Hoon

    1998-01-01

    The purpose of this study is to evaluate the utility of renal CT scanning and to histologically correlate renal damage induced by renal arterial infusion of 0.2 ml/kg of doxorubicin-lipiodol emulsion. Renal CT scans of 20 rabbit kidneys were obtained 15 days after transcatheter arterial chemoembolization and were classified into four grades, as follows: grade 0 - no fleck, grade 1 - one to three nodular flecks; grade 2 - four or more nodular flecks, or one semilunar fleck; and grade 3 - two or more semilunar flecks. The percentage of histological section occupied by lesion was determined using squared paper, and compared with the grades determined on the basis of CT. The histologic findings were interstitial inflammatory cell infiltration, intratubular lipiodol droplets, dystrophic calcification, and and cellular necrosis. The mean sizes of grade 0, 1, 2 and 3 histological lesions were 2.2 % (n=5), 4.5 % (n=4), 21.9 % (n=7), and 24% (n=4), respectively. Grades 0 and 1 accounted for nine cases (3.2%), while grades 2 and 3 accounted for 11 (22.6%); this difference was statistically significant (p<0.01). CT findings showing nodular or semilunar flecks 15 days after infusion into the renal artery of doxorubicin-lipiodol emulsion correlate with the size of the damaged kidney, as seen on histological specimens. (author). 19 refs., 3 tabs., 5 figs

  9. Role of fibronectin under conditions of doxorubicin action

    Directory of Open Access Journals (Sweden)

    A. I. Shevtsova

    2015-02-01

    Full Text Available There is no standard as to treatment of anthracycline chemotherapy complications. The reduction of cytotoxic drugs toxicity without weakening of their antitumor action remains relevant. The extracellular matrix which key component is fibronectin is present in all tissues and it continuously undergoes controlled remodeling. So, the purpose of our work was to study the level of fibronectin in the experimental model of doxorubicin-induced cardiomyopathy and effects of this cytostatic and its co-administration with antioxidants of different nature.The level of fibronectin was measured by ELISA using monospecific antibodies against fibronectin (Sigma, USA, secondary anti-IgG labeled with horseradish peroxidase (Sigma, USA and fibronectin standard (Sigma, USA. The study was conducted on Wistar male rats with weight of 210 ± 50 g which were divided into 4 groups by 8 animals in each group: 1 – control, rats receiving saline i/p; 2 – doxorubicin 1 mg/kg i/p once a week during 4 weeks; 3 – doxorubicin by the same scheme plus 1% 2-oxoglutarate in drinking water during 4 weeks;4 – doxorubicin by the same scheme and korvitin injection 30 min before doxorubicin application once a week during 4 weeks. Obtained data indicate the effect of doxorubicin to decrease in index mass heart in 38% of animals compared to control animals; decrease in total protein concentration by 8% (Р < 0,05 and increase of the level of fibronectin by 67% (P < 0,001 in blood plasma of rats and decrease in the level of fibronectin in the heart extract by 19% (Р < 0,05 under development of doxorubicin-induced cardiotoxicity. Increased fibronectin concentration in blood plasma had strong correlation with decreased total protein concentration in blood (r=0,80 and heart extract (r=0,59 in rats with doxorubicin-induced cardiomiophaty indicating the sensitive reaction of fibronectin to development of metabolic disorders under doxorubicin influence.

  10. Early and late arrhythmogenic effects of doxorubicin.

    Science.gov (United States)

    Kilickap, Saadettin; Barista, Ibrahim; Akgul, Ebru; Aytemir, Kudret; Aksoy, Sercan; Tekuzman, Gulten

    2007-03-01

    To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens. A prospective study including 29 patients who were treated with doxorubicin-containing regimens. Cardiac evaluation was based on 24-hour electrocardiographic monitorization (Holter), which was performed during the first cycle of doxorubicin-containing regimens, as well as after the last cycle of chemotherapy. The mean age of the patients was 45.8 +/- 15.1 (range 18-69). Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients (65.5%) and in 18 (62.1%) patients after completion of therapy. One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated. The patient subsequently underwent permanent pacemaker implantation. Doxorubicin may result in arrhythmias both in early and late periods of treatment. These arrhythmias are rarely life threatening.

  11. Effect of corticosteroids on phlebitis induced by intravenous infusion of antineoplastic agents in rabbits.

    Science.gov (United States)

    Kohno, Emiko; Murase, Saori; Matsuyama, Kenji; Okamura, Noboru

    2009-08-06

    Phlebitis caused by intravenous infusion of antineoplastic agents is one of the critical problems when anticancer therapy is prolonged. We have already reported that both rapid infusion and dilution of the injection solution were effective methods for reducing phlebitis caused by vinorelbine (VNR) in rabbits. The aim of this study was to explore other practical methods for preventing phlebitis caused by VNR and doxorubicin (DXR) in a rabbit model. VNR is often used with cisplatin, and dexamethasone (DEX) has been co-administered for prevention of cisplatin-induced nausea. DXR is used with prednisolone (PSL) in the CHOP regimen for the treatment of non-Hodgkin's lymphoma. Therefore, the present study investigated the prevention of phlebitis due to VNR with DEX and that due to DXR with PSL. VNR and DXR were diluted with normal saline to prepare test solutions at concentrations of 0.6 mg/mL and 1.4 mg/mL, respectively. Each test solution was infused into the auricular veins of rabbits. Two days after VNR infusion and three days after DXR infusion, the veins were evaluated histopathologically. The effect of DEX on VNR-induced phlebitis was evaluated by infusion of DEX before or after VNR. The effect of PSL on DXR-induced phlebitis was similarly evaluated by co-infusion of PSL. The histopathological features of phlebitis caused by the antineoplastic agents differed between VNR and DXR: VNR did not cause the loss of venous endothelial cells, but caused inflammatory cell infiltration, edema, and epidermal degeneration. In contrast, DXR caused the loss of venous endothelial cells and chrondrocyte necrosis. Pre-treatment and post-treatment with DEX significantly decreased VNR-induced phlebitis compared with the control group and pre-treatment was particularly effective. Co-infusion of PSL also significantly decreased phlebitis caused by DXR, but its effect was less marked. The present findings suggested that pre-treatment with DEX may be a useful method for preventing

  12. The magnetoviscous effect of micellar solutions doped with water based ferrofluids

    Energy Technology Data Exchange (ETDEWEB)

    Arantes, Fabiana R., E-mail: farantes@if.usp.br [Institute of Physics, University of Sao Paulo (Brazil); Institute of Fluid Mechanics, Technische Universität Dresden (Germany); Odenbach, Stefan, E-mail: stefan.odenbach@tu-dresden.de [Institute of Fluid Mechanics, Technische Universität Dresden (Germany)

    2015-09-15

    This work presents a magnetorheological study of micellar solutions of potassium laurate and water doped with magnetite nanoparticles, accompanied by auxiliary dynamic light scattering measurements. An increase in the viscosity of the samples under applied field was observed and, furthermore, a considerable magnetoviscous effect was revealed even at magnetic particles' concentrations as low as 0.005–0.01 vol%. This indicates that the rheological behavior of the micelles is changed by the interaction of the magnetic particles with the applied field, leading to different microscopic arrangements in the micellar solutions. - Highlights: • We study the magnetorheological behavior of micellar solutions doped with ferrofluids. • We observe an increase in the viscosity of the samples under an applied field. • We find a large magnetoviscous effect even at low magnetic particles' concentration. • Interaction of particles with the field changes the micelles' rheological behavior.

  13. Molecular motion of micellar solutes: a 13C NMR relaxation study

    International Nuclear Information System (INIS)

    Stark, R.E.; Kasakevich, M.L.; Granger, J.W.

    1982-01-01

    A series of simple NMR relaxation experiments have been performed on nitrobenzene and aniline dissolved in the ionic detergents sodium dodecyl sulfate (SDS) and hexadecyltrimethylammonium bromide (CTAB). Using 13 C relaxation rates at various molecular sites, and comparing data obtained in organic media with those for micellar solutions, the viscosity at the solubilization site was estimated and a detailed picture of motional restrictions imposed by the micellar enviroment was derived. Viscosities of 8 to 17 cp indicate a rather fluid environment for solubilized nitrobenzene; both additives exhibit altered motional preferences in CTAB solutions only. As an aid in interpretation of the NMR data, quasi-elastic light scattering and other physical techniques have been used to evaluate the influence of organic solutes on micellar size and shape. The NMR methods are examined critically in terms of their general usefulness for studies of solubilization in detergent micelles. 48 references

  14. Stepwise dynamics of an anionic micellar film - Formation of crown lenses.

    Science.gov (United States)

    Lee, Jongju; Nikolov, Alex; Wasan, Darsh

    2017-06-15

    We studied the stepwise thinning of a microscopic circular foam film formed from an anionic micellar solution of sodium dodecyl sulfate (SDS). The foam film formed from the SDS micellar solution thins in a stepwise manner by the formation and expansion of a dark spot(s) of one layer less than the film thickness. During the last stages of film thinning (e.g., a film with one micellar layer), the dark spot expansion occurs via two steps. Initially, a small dark circular spot inside a film of several microns in size is formed, which expands at a constant rate. Then, a ridge along the expanding spot is formed. As the ridge grows, it becomes unstable and breaks into regular crown lenses, which are seen as white spots in the reflected light at the border of the dark spot with the surrounding thicker film. The Rayleigh type of instability contributes to the formation of the lenses, which results in the increase of the dark spot expansion rate with time. We applied the two-dimensional micellar-vacancy diffusion model and took into consideration the effects of the micellar layering and film volume on the rate of the dark spot expansion [Lee et al., 2016] to predict the rate of the dark spot expansion for a 0.06M SDS film in the presence of lenses. We briefly discuss the Rayleigh type of instability in the case of a 0.06M SDS foam film. The goals of this study are to reveal why the crown lenses are formed during the foam film stratification and to elucidate their effect on the rate of spot expansion. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Selection of reservoirs amenable to micellar flooding. First annual report, October 1978-December 1979

    Energy Technology Data Exchange (ETDEWEB)

    Goldburg, A.; Price, H.

    1980-12-01

    The overall project objective is to build a solid engineering base upon which the Department of Energy (DOE) can improve and accelerate the application of micellar-polymer recovery technology to Mid-Continent and California sandstone reservoirs. The purpose of the work carried out under these two contracts is to significantly aid, both DOE and the private sector, in gaining the following Project Objectives: to select the better micellar-polymer prospects in the Mid-Continent and California regions; to assess all of the available field and laboratory data which has a bearing on recovering oil by micellar-polymer projects in order to help identify and resolve both the technical and economic constraints relating thereto; and to design and analyze improved field pilots and tests and to develop a micellar-polymer applications matrix for use by the potential technology users; i.e., owner/operators. The report includes the following: executive summary and project objectives; development of a predictive model for economic evaluation of reservoirs; reservoir data bank for micellar-polymer recovery evaluation; PECON program for preliminary economic evaluation; ordering of candidate reservoirs for additional data acquisition; validation of predictive model by numerical simulation; and work forecast. Tables, figures and references are included.

  16. Micellar liquid chromatography

    International Nuclear Information System (INIS)

    Basova, Elena M; Ivanov, Vadim M; Shpigun, Oleg A

    1999-01-01

    Background and possibilities of practical applications of micellar liquid chromatography (MLC) are considered. Various retention models in MLC, the effects of the nature and concentration of surfactants and organic modifiers, pH, temperature and ionic strength on the MLC efficiency and selectivity are discussed. The advantages and limitations of MLC are demonstrated. The performance of MLC is critically evaluated in relationship to the reversed-phase HPLC and ion-pair chromatography. The potential of application of MLC for the analysis of pharmaceuticals including that in biological fluids and separation of inorganic anions, transition metal cations, metal chelates and heteropoly compounds is described. The bibliography includes 146 references.

  17. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    International Nuclear Information System (INIS)

    Henninger, Christian; Huelsenbeck, Johannes; Huelsenbeck, Stefanie; Grösch, Sabine; Schad, Arno; Lackner, Karl J.; Kaina, Bernd; Fritz, Gerhard

    2012-01-01

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  18. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, Christian [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany); Huelsenbeck, Johannes; Huelsenbeck, Stefanie [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Grösch, Sabine [Institute of Clinical Pharmacology, Johann Wolfgang Goethe University Frankfurt, Theodor Stern Kai 7, D-60590 Frankfurt/Main (Germany); Schad, Arno [Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Lackner, Karl J. [Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Kaina, Bernd [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany)

    2012-05-15

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  19. Molecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Menglin Cheng

    2017-08-01

    Full Text Available Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS detected total choline (tCho signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC, phosphocholine (PC and free choline (Cho, before and after treatment with the commonly used chemotherapeutic drug doxorubicin in weakly metastatic human MCF7 and triple-negative human MDA-MB-231 breast cancer cells. While the tCho concentration did not change following doxorubicin treatment, GPC significantly increased and PC decreased. Of the two phosphatidylcholine-specific PLD enzymes, only PLD1, but not PLD2, mRNA was down-regulated by doxorubicin treatment. For the two reported genes encoding GPC phosphodiesterase, the mRNA of GDPD6, but not GDPD5, decreased following doxorubicin treatment. mRNA levels of choline kinase α (ChKα, which converts Cho to PC, were reduced following doxorubicin treatment. PLD1 and ChKα protein levels decreased following doxorubicin treatment in a concentration dependent manner. Treatment with the PLD1 specific inhibitor VU0155069 sensitized MCF7 and MDA-MB-231 breast cancer cells to doxorubicin-induced cytotoxicity. Low concentrations of 100 nM of doxorubicin increased MDA-MB-231 cell migration. GDPD6, but not PLD1 or ChKα, silencing by siRNA abolished doxorubicin-induced breast cancer cell migration. Doxorubicin induced GPC increase and PC decrease are caused by reductions in PLD1, GDPD6, and ChKα mRNA and protein expression. We have shown that silencing or inhibiting these genes/proteins can promote drug effectiveness and reduce adverse drug effects. Our findings emphasize the importance of detecting PC and GPC individually.

  20. Transarterial chemoembolization using gelatin sponges or microspheres plus lipiodol-doxorubicin versus doxorubicin-loaded beads for the treatment of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Liu, Yi Sheng; Ou, Ming Ching; Tsai, Yi Shan; Lin, Xi Zhang; Wang, Chien Kuo; Tsai, Hong Ming; Chuang, Ming Tsung

    2015-01-01

    To retrospectively compare treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) using gelatin sponges or microspheres plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB). A total of 158 patients with HCC received TACE from November 2010 to November 2011 were enrolled in this study, including 64 (40.5%) received TACE with lipiodol-doxorubicin and gelatin sponges (group A), 41 (25.9%) received TACE with lipiodol-doxorubicin and microspheres (group B), and 53 (33.5%) received TACE with doxorubicin-loaded DEB (group C). Tumor response and adverse events (AEs) were evaluated. No significant difference was found at baseline among the three groups. The doxorubicin dosage in group C was significantly (p < 0.001) higher compared to the dose used in groups A or B (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in group C achieved complete response compared to those in groups A or B (32.1% vs. 6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs were more common in groups A and B compared to group C, with rates of 54.7%, 34.1%, and 5.7%, respectively. In patients with HCC, TACE with DEB offers better safety and efficacy profiles compared to either TACE with gelatin sponges or TACE with microspheres.

  1. INFLUENCE OF DOXORUBICIN ON ADHESIVE PROPERTIES OF E.COLI

    Directory of Open Access Journals (Sweden)

    O.G. Shapoval

    2008-09-01

    Full Text Available Influence ofantineoplastic drug doxorubicin and amikacin, the aminoglycoside family on adhesive activity of Escherichia coli was studied. Antimicrobialactivity(minimum inhibitory concentration-MIC ofboth drugs against experimental strains using serial two-fold dilution method was determined. Susceptibility of E.coli to amikacin in the presence of Sand j MIC doxorubicin was studied. After 10 passages in beef-extract broth with constant and increasing doxorubicin concentrations in the presence of Sand j MIC doxorubicin, the adhesive activity of initial and passage variants according to theirability to absorb human erythrocytes 1(0 Rh+ was determined. Itwas observed that experimental strains were susceptible to amikacin (MIC 1,5-6,2 mkg/ml butwere resistantto doxorubicin (MIC 1000 mkg/ml. Subinhibitory concentrations of this cytostatic (S and j MIC raised the sensitivity of experimental strains to amikacin and differently effected on adhesive activity of passage variants of E.coli.

  2. Morbidity of a combined modality therapy of I.A. Doxorubicin, neoadjuvant radiotherapy and surgery for locally advanced high grade Soft Tissue Sarcomas (STS) of the extremities

    International Nuclear Information System (INIS)

    Nijhuis, Paul; Pras, Betty; Sleijfer, Dirk Th.; Molenaar, Ineke M.; Schraffordt, Koops Heimen; Hoekstra, Harald J.

    1997-01-01

    Purpose/objective: In the early eighties a combined modality therapy of intra-arterial doxorubicin, neo-adjuvant radiotherapy and surgery was introduced as limb-saving treatment for 'unresectable' grade III high grade STS of the extremities. We studied short and long-term morbidity of this combined modality treatment. Materials and methods: Between 1982 and 1986 11 patients, 9 male and 2 female, median age 52 (range 24-70) years, with 'unresectable' grade III STS of the extremities were treated by preoperative i.a. infusion of doxorubicin for three consecutive days (daily dose 20 mg/m 2 ). Within 24 hours after infusion preoperative radiation of the compartment (10 x 350 cGy) was started. After chemo-radiotherapy the tumor was resected. Non-radical resections received additionally 20-30 Gy radiotherapy (9 patients). Results: No local recurrences (median follow-up 110 months); pulmonary metastases in five patients (45%). Local skin toxicity due to doxorubicin in three patients (27%). Preoperative 35 Gy radiotherapy was well tolerated. Limb-saving treatment was possible in ten patients (91%); in one patient an exarticulation of the hip had to be performed. Three of the five long-term survivors (follow-up > 10 years) developed a severe fibrosis of the affected limb (60%). Two severe long-term complications: a stress fracture of the affected femur (91 months after treatment), and a severe radiation-induced motor and sensory neuropathy of the sciatic nerve. Conclusion: The long-term results show a limb-saving rate of 91%, without increasing the risk of a local recurrence. Especially the long-term morbidity is extremely high (60%). This combination therapy should therefore no longer be advocated as a limb-saving treatment modality for these primarily 'unresectable' high grade STS of the extremities

  3. Encapsulation and covalent binding of molecular payload in enzymatically activated micellar nanocarriers.

    Science.gov (United States)

    Rosenbaum, Ido; Harnoy, Assaf J; Tirosh, Einat; Buzhor, Marina; Segal, Merav; Frid, Liat; Shaharabani, Rona; Avinery, Ram; Beck, Roy; Amir, Roey J

    2015-02-18

    The high selectivity and often-observed overexpression of specific disease-associated enzymes make them extremely attractive for triggering the release of hydrophobic drug or probe molecules from stimuli-responsive micellar nanocarriers. Here we utilized highly modular amphiphilic polymeric hybrids, composed of a linear hydrophilic polyethylene glycol (PEG) and an esterase-responsive hydrophobic dendron, to prepare and study two diverse strategies for loading of enzyme-responsive micelles. In the first type of micelles, hydrophobic coumarin-derived dyes were encapsulated noncovalently inside the hydrophobic core of the micelle, which was composed of lipophilic enzyme-responsive dendrons. In the second type of micellar nanocarrier the hydrophobic molecular cargo was covalently linked to the end-groups of the dendron through enzyme-cleavable bonds. These amphiphilic hybrids self-assembled into micellar nanocarriers with their cargo covalently encapsulated within the hydrophobic core. Both types of micelles were highly responsive toward the activating enzyme and released their molecular cargo upon enzymatic stimulus. Importantly, while faster release was observed with noncovalent encapsulation, higher loading capacity and slower release rate were achieved with covalent encapsulation. Our results clearly indicate the great potential of enzyme-responsive micellar delivery platforms due to the ability to tune their payload capacities and release rates by adjusting the loading strategy.

  4. Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

    Science.gov (United States)

    Moruno-Manchon, Jose F; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

    2018-01-01

    Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

    Science.gov (United States)

    Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

    2010-10-01

    Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

  6. Photonics of dyes molecules in reverse micellar solution

    International Nuclear Information System (INIS)

    Ibragimova, M.R.; Laurinas, V.Ch.

    2001-01-01

    Spectral luminescent characteristics of the dye acridine orange and eosin has been studied in reverse micellar solutions of sodium bis(2-ethyl-hexyl)sulfosuccinate. It was shown that the increase of the nucleus volume of reverse micelles. (author)

  7. Increased Dietary Leucine Reduces Doxorubicin-Associated Cardiac Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Thiago M. Fidale

    2018-01-01

    Full Text Available Cardiotoxicity is one of the most significant adverse effects of the oncologic treatment with doxorubicin, which is responsible for a substantial morbid and mortality. The occurrence of heart failure with ventricular dysfunction may lead to severe cardiomyopathy and ultimately to death. Studies have focused on the effects of leucine supplementation as a strategy to minimize or revert the clinical condition of induced proteolysis by several clinical onsets. However, the impact of leucine supplementation in heart failure induced by doxorubicin is unknown. Therefore, the objective of this work is to evaluate the effects of leucine supplementation on the cardiotoxicity in the heart of rats treated with doxorubicin. Rats treated with a 7.5 mg/kg cumulative dose of doxorubicin for 14 days presented a dilatation of the left ventricle (LV, and a reduction of the ejection fraction (FE. The 5% supplementation of leucine in the rats' food prevented the malfunctioning of the LV when administered with doxorubicin. Some alterations in the extracellular matrix remodeling were confirmed by the increase of collagen fibers in the doxorubicin group, which did not increase when the treatment was associated with leucine supplementation. Leucine attenuates heart failure in this experimental model with doxorubicin. Such protection is followed by the maintenance of interstitial collagen fibers.

  8. Modification of silica surface by gamma ray induced Ad micellar Polymerization

    International Nuclear Information System (INIS)

    Buathong, Salukjit; Pongprayoon, Thirawudh; Suwanmala, Phiriyatorn

    2005-10-01

    Precipitated silica is often added to natural rubber compounds in order to improve performance in commercial application. A problem with using silica as filler is the poor compatibility between silica and natural rubber. In this research, polyisoprene was coated on silica surface by gamma ray induced ad micellar polymerization in order to achieve the better compatibility between silica and natural rubber. The modified silica was characterized by FT-IR, and SEM. The results show that polyisoprene was successfully coated on silica surface via gamma ray induced ad micellar polymerization

  9. Visible-light system for detecting doxorubicin contamination on skin and surfaces.

    Science.gov (United States)

    Van Raalte, J; Rice, C; Moss, C E

    1990-05-01

    A portable system that uses fluorescence stimulated by visible light to identify doxorubicin contamination on skin and surfaces was studied. When activated by violet-blue light in the 465-nm range, doxorubicin fluoresces, emitting orange-red light in the 580-nm range. The light source to stimulate fluorescence was a slide projector with a filter to selectively pass short-wave (blue) visible light. Fluorescence was both observed visually with viewing spectacles and photographed. Solutions of doxorubicin in sterile 0.9% sodium chloride injection were prepared in nine standard concentrations ranging from 2 to 0.001 mg/mL. Droplets of each admixture were placed on stainless steel, laboratory coat cloth, pieces of latex examination glove, bench-top absorbent padding, and other materials on which antineoplastics might spill or leak. These materials then were stored for up to eight weeks and photographed weekly. The relative ability of water, household bleach, hydrogen peroxide solution, and soap solution to deactivate doxorubicin was also measured. Finally, this system was used to inspect the antineoplastic-drug preparation and administration areas of three outpatient cancer clinics for doxorubicin contamination. Doxorubicin fluorescence was easily detectable with viewing spectacles when a slide projector was used as the light source. The photographic method was sensitive for doxorubicin concentrations from 2.0 to 0.001 mg/mL. Immersion of study materials in bleach for one minute eliminated detectable fluorescence. Doxorubicin contamination is detectable for at least eight weeks in the ambient environment. Probable doxorubicin contamination was detected in two of the three clinics surveyed. A safe, portable system that uses fluorescence stimulated by visible light is a sensitive method for detecting doxorubicin on skin and surfaces.

  10. Redox reactions in micellar systems. communication 4. Eosin-photosensitized reduction of methylviologen

    Energy Technology Data Exchange (ETDEWEB)

    Nadtochenko, V.; Dzhabiev, T.S.; Rubtsov, I.V.

    1985-12-10

    The authors present data on photosensitized reduction of methylviologen (MV/sup 2 +/) by disodium ethylenediaminetetraacetate (EDTA) in micellar systems modeling, in a first approximation, the structural organization of components of the chain of energy and electron transfer in natural photosynthesis. Photosensitized reduction of methylviologen by EDTA in micellar solutions can model photosystem I of plants with structure formation of reagents and transfer of excitation energy before the step of occurrence of a redox reaction in the active center.

  11. Effect of ripening, heat processing, and fat type on the micellarization of pigments from jalapeño peppers.

    Science.gov (United States)

    Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús; Yahia, Elhadi M; Jiménez-Castro, Jorge A; Cervantes-Paz, Braulio; Ibarra-Junquera, Vrani; Pérez-Martínez, Jaime David; Zamudio-Flores, Paul B; Escalante-Minakata, Pilar

    2013-10-16

    Raw and heat-processed (boiled and grilled) jalapeño peppers at three intermediate ripening stages (brown, 50% red, and 75% red) were digested in vitro without fat and in the presence of soybean oil (SO) or beef tallow (BT), and the micellarization of their lipid soluble pigments (LSP) was measured. The micelles from digestions with brown, 50% red, and 75% red peppers contained up to 27, 35, and 29 different LSP, respectively. Boiling and grilling decreased the micellarization of LSP from brown peppers, whereas the opposite was observed with 75% red peppers. Heat processing did not clearly affect the micellarization of LSP from 50% red fruits. The impact of fat on LSP micellarization was ripening-dependent, but the micellarization of the less polar carotenoids was always increased by SO or BT. This positive effect of fat was higher with SO than with BT.

  12. First Example of a Lipophilic Porphyrin-Cardanol Hybrid Embedded in a Cardanol-Based Micellar Nanodispersion

    Directory of Open Access Journals (Sweden)

    Giuseppe Vasapollo

    2012-10-01

    Full Text Available Cardanol is a natural and renewable organic raw material obtained as the major chemical component by vacuum distillation of cashew nut shell liquid. In this work a new sustainable procedure for producing cardanol-based micellar nanodispersions having an embedded lipophilic porphyrin itself peripherally functionalized with cardanol substituents (porphyrin-cardanol hybrid has been described for the first time. In particular, cardanol acts as the solvent of the cardanol hybrid porphyrin and cholesterol as well as being the main component of the nanodispersions. In this way a “green” micellar nanodispersion, in which a high percentage of the micellar system is derived from renewable “functional” molecules, has been produced.

  13. Doxorubicin Action on Mitochondria: Relevance to Osteosarcoma Therapy?

    Science.gov (United States)

    Armstrong, Jo; Dass, Crispin R

    2018-01-01

    The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used clinically as frontline therapy. This same mechanism of cell inhibition is also pertinent to doxorubicin's primary cause of side-effects, that to the cardiac tissue, culminating in such dire events as congestive heart failure. Reactive oxygen species are partly to blame for this effect on the mitochondria, which impact the electron transport chain. As this review highlights that, there is much more to be learnt about the mitochondria and how it is affected by such effective but toxic drugs as doxorubicin. Such information will aid researchers who search for cancer treatment able to preserve mitochondrial number and function in normal cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Histopathological effects of doxorubicin on kidneys in rats

    Directory of Open Access Journals (Sweden)

    I.A. Ali

    2014-06-01

    Full Text Available The aim of this study was to investigate the histolopathological effect of doxorubicin on rat kidney tissue. The drug was administrated by rats at the dose of (1, 2, 3, 4, 5 mg/kg intrapertonial every (84 hr for the three weeks and the doses of (1, 2, 3 mg/kg intrapertonial every 84 hrs for six weeks. The animals were scarified after 48 hr. of last injection. The study revealed congestion, thrombus, blood vessels hemorrhage, vaculation in the cells of glomerular tuft and tubular, tubuo-interstitial degeneration, tubular casts. The injury score revealed significantly increasing in the degree of injury in glomerules in the animals that received 5 mg/kg of doxorubicin for three weeks and also significantly increasing in the degree of injury in glomerules of the animals that received 3 mg/kg of doxorubicin for six weeks as compared with control animals. We concluded that the doxorubicin has histopathological effect on kidney.

  15. Identification of CREB3L1 as a Biomarker Predicting Doxorubicin Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Bray Denard

    Full Text Available Doxorubicin has been shown to inhibit proliferation of cancer cells through proteolytic activation of CREB3L1 (cAMP response element binding protein 3-like 1, a transcription factor synthesized as a membrane-bound precursor. Upon doxorubicin treatment, CREB3L1 is cleaved so that the N-terminal domain of the protein can reach the nucleus where it activates transcription of genes that inhibit cell proliferation. These results suggest that the level of CREB3L1 in cancer cells may determine their sensitivity to doxorubicin.Mice transplanted with 6 lines of renal cell carcinoma (RCC were injected with doxorubicin to observe the effect of the chemotherapy on tumor growth. Immunohistochemistry and bioinformatics analyses were performed to compare CREB3L1 levels in types of cancer known to respond to doxorubicin versus those resistant to doxorubicin.Higher levels of CREB3L1 protein are correlated with increased doxorubicin sensitivity of xenograft RCC tumors (p = 0.017 by Pearson analysis. From patient tumor biopsies we analyzed, CREB3L1 was expressed in 19% of RCC, which is generally resistant to doxorubicin, but in 70% of diffuse large B-cell lymphoma that is sensitive to doxorubicin. Doxorubicin is used as the standard treatment for cancers that express the highest levels of CREB3L1 such as osteosarcoma and malignant fibrous histiocytoma but is not generally used to treat those that express the lowest levels of CREB3L1 such as RCC.Identification of CREB3L1 as the biomarker for doxorubicin sensitivity may markedly improve the doxorubicin response rate by applying doxorubicin only to patients with cancers expressing CREB3L1.

  16. Fundamental Characterization of the Micellar Self-Assembly of Sophorolipid Esters.

    Science.gov (United States)

    Koh, Amanda; Todd, Katherine; Sherbourne, Ezekiel; Gross, Richard A

    2017-06-13

    Surfactants are ubiquitous constituents of commercial and biological systems that function based on complex structure-dependent interactions. Sophorolipid (SL) n-alkyl esters (SL-esters) comprise a group of modified naturally derived glycolipids from Candida bombicola. Herein, micellar self-assembly behavior as a function of SL-ester chain length was studied. Surface tensions as low as 31.2 mN/m and critical micelle concentrations (CMCs) as low as 1.1 μM were attained for diacetylated SL-decyl ester (dASL-DE) and SL-octyl ester, respectively. For deacetylated SL-esters, CMC values reach a lower limit at SL-ester chains above n-butyl (SL-BE, 1-3 μM). This behavior of SL-esters with increasing hydrophobic tail length is unlike other known surfactants. Diffusion-ordered spectroscopy (DOSY) and T 1 relaxation NMR experiments indicate this behavior is due to a change in intramolecular interactions, which impedes the self-assembly of SL-esters with chain lengths above SL-BE. This hypothesis is supported by micellar thermodynamics where a disruption in trends occurs at n-alkyl ester chain lengths above those of SL-BE and SL-hexyl ester (SL-HE). Diacetylated (dA) SL-esters exhibit an even more unusual trend in that CMC increases from 1.75 to 815 μM for SL-ester chain lengths of dASL-BE and dASL-DE, respectively. Foaming studies, performed to reveal the macroscopic implications of SL-ester micellar behavior, show that the observed instability in foams formed using SL-esters are due to coalescence, which highlights the importance of understanding intermicellar interactions. This work reveals that SL-esters are an important new family of green high-performing surfactants with unique structure-property relationships that can be tuned to optimize micellar characteristics.

  17. Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yeh, Y.C. [Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi, Taiwan (China); Wang, L.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Ting, C.T.; Lee, W.L. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Lee, H.W. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, K.Y. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan (China); Wu, A. [College of Biological Science, University of California, Davis (United States); Su, C.S. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Liu, T.J., E-mail: trliu@vghtc.gov.tw [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

    2011-12-15

    Background: Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. Methods: Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1 {mu}M), propofol (1 {mu}M), or propofol plus doxorubicin (given 1 h post propofol). After 24 h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. Results: Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-{delta} was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. Conclusions: Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application. -- Highlights: Black-Right-Pointing-Pointer We evaluate how propofol prevents doxorubicin-induced toxicity in cardiomyocytes. Black-Right-Pointing-Pointer Propofol reduces doxorubicin-imposed nitrative and oxidative stress. Black-Right-Pointing-Pointer Propofol suppresses mitochondrion-, p53- and PKC-related apoptotic signaling. Black-Right-Pointing-Pointer Propofol ameliorates apoptosis and

  18. Antioxidant activities of celery and parsley juices in rats treated with doxorubicin.

    Science.gov (United States)

    Kolarovic, Jovanka; Popovic, Mira; Zlinská, Janka; Trivic, Svetlana; Vojnovic, Matilda

    2010-09-03

    We have examined the influence of diluted pure celery and parsley leaf and root juices and their combinations with doxorubicin on the antioxidant status [as measured by the content of reduced glutathione (GSH) and ferric reducing antioxidant power (FRAP)] in liver homogenate and hemolysate and on the contents of cytochrome P450 in liver homogenate. It was found that doxorubicin significantly decreased the content of reduced glutathione and the total antioxidative status (FRAP) in liver homogenate and hemolysate, while celery and parsley juices alone and in combination with doxorubicin had different actions. Doxorubicin and celery juice had no effect on content of cytochrome P450. However, in combination with doxorubicin, parsley root juice significant increased, and parsley leaves juice decreased the cytochrome P450 content (compared to doxorubicin treated animals). Only parsley root juice significantly increased the content of cytochrome P450.

  19. Effect of the interaction of heat-processing style and fat type on the micellarization of lipid-soluble pigments from green and red pungent peppers (Capsicum annuum).

    Science.gov (United States)

    Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús; Yahia, Elhadi M; Failla, Mark L

    2013-04-17

    The high diversity of carotenoids and chlorophylls in foods contrasts with the reduced number of pigments that typically are investigated in micellarization studies. In this study, pepper samples (raw and heat-treated) contained 68 individual pigments, but only 38 of them were micellarized after in vitro digestion. The micellarization of pigments was majorly determined by the interaction effect of processing style (food matrix effect) and fat type (saturated and unsaturated). The highest micellarization was observed with raw peppers. Unsaturated fat increased the micellarization of carotenoid esters, while the impact of fat on the micellarization of free carotenoids seemed to be dependent on pigment structure. The micellarization efficiency was diminished as the esterification level of carotenoids increased. The type of fatty acid moiety and the polarity of the carotenoids modulated their micellarization. Chlorophylls were transformed into pheophytins by heat-processing and digestion, with the pheophytins being stable under gastrointestinal conditions. Micellarization of pheophytins was improved by fat.

  20. Lateral Order and Self-Organized Morphology of Diblock Copolymer Micellar Films

    Directory of Open Access Journals (Sweden)

    Jiun-You Liou

    2018-05-01

    Full Text Available We report the lateral order and self-organized morphology of diblock copolymer polystyrene-block-poly(2-vinylpyridine, P(S-b-2VP, and micelles on silicon substrates (SiOx/Si. These micellar films were prepared by spin coating from polymer solutions of varied concentration of polymer in toluene onto SiOx/Si, and were investigated with grazing-incidence small-angle X-ray scattering (GISAXS and an atomic force microscope (AFM. With progressively increased surface coverage with increasing concentration, loosely packed spherical micelles, ribbon-like nanostructures, and a second layer of spherical micelles were obtained sequentially. Quantitative analysis and simulations of the micellar packing demonstrates that the spatial ordering of the loosely packed spherical micelles altered from short-range order to hexagonal order when the micellar coverage increased from small to moderate densities of the covered surface. At large densities, anisotropic fusion between spherical micelles caused the ribbon-like nanostructures to have a short-range spatial order; the ordering quality of the second layer was governed by the rugged surface of the underlying layer because the valleys between the ribbon-like nanostructures allowed for further deposition of spherical micelles.

  1. Glutathione transferase mimics : Micellar catalysis of an enzymic reaction

    NARCIS (Netherlands)

    Lindkvist, Björn; Weinander, Rolf; Engman, Lars; Koetse, Marc; Engberts, Jan B.F.N.; Morgenstern, Ralf

    1997-01-01

    Substances that mimic the enzyme action of glutathione transferases (which serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nitroarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic

  2. TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin

    Science.gov (United States)

    Moruno Manchon, Jose Felix; Uzor, Ndidi-Ese; Kesler, Shelli R.; Wefel, Jeffrey S.; Townley, Debra M.; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S.; Sood, Anil K.; Tsvetkov, Andrey S.

    2016-01-01

    Doxorubicin, a commonly used chemotherapy agent, induces severe cardio- and neurotoxicity. Molecular mechanisms of cardiotoxicity have been extensively studied, but mechanisms by which doxorubicin exhibits its neurotoxic properties remain unclear. Here, we show that doxorubicin impairs neuronal autophagy, leading to the accumulation of an autophagy substrate p62. Neurons treated with doxorubicin contained autophagosomes, damaged mitochondria, and lipid droplets. The brains from mice treated with pegylated liposomal doxorubicin exhibited autophagosomes, often with mitochondria, lipofuscin, and lipid droplets. Interestingly, lysosomes were less acidic in doxorubicin-treated neurons. Overexpression of the transcription factor EB (TFEB), which controls the autophagy-lysosome axis, increased survival of doxorubicin-treated neurons. 2-Hydroxypropyl-β-cyclodextrin (HPβCD), an activator of TFEB, also promoted neuronal survival, decreased the levels of p62, and lowered the pH in lysosomes. Taken together, substantial changes induced by doxorubicin contribute to neurotoxicity, cognitive disturbances in cancer patients and survivors, and accelerated brain aging. The TFEB pathway might be a new approach for mitigating damage of neuronal autophagy caused by doxorubicin. PMID:27992857

  3. The same drug but a different mechanism of action: comparison of free doxorubicin with two different N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugates in EL-4 cancer cell line.

    Science.gov (United States)

    Kovár, Lubomír; Strohalm, Jirí; Chytil, Petr; Mrkvan, Tomás; Kovár, Marek; Hovorka, Ondrej; Ulbrich, Karel; Ríhová, Blanka

    2007-01-01

    Doxorubicin is one of the most potent anti-tumor drugs with a broad spectrum of use. To reduce its toxic effect and improve its pharmacokinetics, we conjugated it to an HPMA copolymer carrier that enhances its passive accumulation within solid tumors via the EPR effect and decreases its cytotoxicity to normal, noncancer cells. In this study, we compared the antiproliferative, pro-survival, and death signals triggered in EL-4 cancer cells exposed to free doxorubicin and doxorubicin conjugated to a HPMA copolymer carrier via either enzymatically (PK1) or hydrolytically (HYD) degradable bonds. We have previously shown that the intracellular distribution of free doxorubicin, HYD, and PK1 is markedly different. Here, we demonstrated that these three agents greatly differ also in the antiproliferative effect and cell death signals they trigger. JNK phosphorylation sharply increased in cells treated with HYD, while treatment with free doxorubicin moderately decreased and treatment with PK1 even strongly decreased it. On the other hand, treatment with free doxorubicin greatly increased p38 phosphorylation, while PK1 and HYD increased it slightly. PK1 also significantly increased ERK phosphorylation, while both the free doxorubicin and HYD conjugate slightly decreased it. Long-term inhibition of JNK significantly increased both proliferation and viability of EL-4 cells treated with free doxorubicin, showing that the JNK signaling pathway could be critical for mediating cell death in EL-4 cells exposed to free doxorubicin. Both activation of caspase 3 and decreased binding activity of the p50 subunit of NFkappaB were observed in cells treated with free doxorubicin and HYD, while no such effects were seen in cells incubated with PK1. Analysis of the expression of genes involved in apoptosis and regulation of the cell cycle demonstrated that free doxorubicin and HYD have very similar mechanisms of action, while PK1 has very different characteristics.

  4. Antioxidant Activities of Celery and Parsley Juices in Rats Treated with Doxorubicin

    Directory of Open Access Journals (Sweden)

    Svetlana Trivic

    2010-09-01

    Full Text Available We have examined the influence of diluted pure celery and parsley leaf and root juices and their combinations with doxorubicin on the antioxidant status [as measured by the content of reduced glutathione (GSH and ferric reducing antioxidant power (FRAP] in liver homogenate and hemolysate and on the contents of cytochrome P450 in liver homogenate. It was found that doxorubicin significantly decreased the content of reduced glutathione and the total antioxidative status (FRAP in liver homogenate and hemolysate, while celery and parsley juices alone and in combination with doxorubicin had different actions. Doxorubicin and celery juice had no effect on content of cytochrome P450. However, in combination with doxorubicin, parsley root juice significant increased, and parsley leaves juice decreased the cytochrome P450 content (compared to doxorubicin treated animals. Only parsley root juice significantly increased the content of cytochrome P450.

  5. Ordering fluctuations in a shear-banding wormlike micellar system

    DEFF Research Database (Denmark)

    Angelico, R.; Rossi, C. Oliviero; Ambrosone, L.

    2010-01-01

    We present a first investigation about the non-linear flow properties and transient orientational-order fluctuations observed in the shear-thinning lecithin–water–cyclohexane wormlike micellar system at a concentration near to the zero-shear isotropic–nematic phase transition. From rheological...

  6. One electron reduction of acridine orange studied in aqueous micellar medium using pulse radiolysis technique

    International Nuclear Information System (INIS)

    Goel, Anjali; Guha, S.N.

    1994-01-01

    Absorption spectrum, decay and formation kinetics of semi reduced species formed by the reaction of hydrated electron (e aq - ) with acridine orange (AO) were evaluated in sodium lauryl sulphate (SLS) micellar medium. Fluorescence and absorption properties of AO were also studied in this micellar system. The results were compared with those in homogenous aqueous medium. (author). 2 refs., 2 figs

  7. Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma

    International Nuclear Information System (INIS)

    Susa, Michiro; Iyer, Arun K; Ryu, Keinosuke; Hornicek, Francis J; Mankin, Henry; Amiji, Mansoor M; Duan, Zhenfeng

    2009-01-01

    Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the efficacy. Doxorubicin was loaded onto a lipid-modified dextran based polymeric nano-system. The effect of various concentrations of doxorubicin alone or nanoparticle loaded doxorubicin on KHOS, KHOS R2 , U-2OS, and U-2OS R2 cells was analyzed. Effects on drug retention, immunofluorescence, Pgp expression, and induction of apoptosis were also analyzed. Dextran nanoparticles loaded with doxorubicin had a curative effect on multidrug resistant osteosarcoma cell lines by increasing the amount of drug accumulation in the nucleus via Pgp independent pathway. Nanoparticles loaded with doxorubicin also showed increased apoptosis in osteosarcoma cells as compared with doxorubicin alone. Lipid-modified dextran nanoparticles loaded with doxorubicin showed pronounced anti-proliferative effects against osteosarcoma cell lines. These findings may lead to new treatment options for MDR osteosarcoma

  8. Study of micellar solutions of the 'sodium lauryl sulphate-heavy water' system by using pulsed NMR

    International Nuclear Information System (INIS)

    Fouchet, C.

    1972-01-01

    This research thesis reports the study of the nuclear magnetic resonance of protons contained by micellar solutions of sodium lauryl sulphate and heavy water. Relaxation times have been measured with respect to various parameters: concentration, temperature, frequency. The author presents the main properties of micellar solutions and indicate the various possible movements. Then, he addresses the implemented technique, and shows that NMR is sensitive to short range interactions, and allows micellar movements to be studied over an extended rate range. Experimental results are then presented and interpreted [fr

  9. Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

    International Nuclear Information System (INIS)

    Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

    2010-01-01

    The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 μM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt max of 105 ± 8 mN/s in control hearts vs. 49 ± 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 ± 0.2 in control hearts vs. 2.2 ± 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 ± 1 μM cytochrome c/min/mg in control hearts vs. 14 ± 3 μM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

  10. INFLUENCE OF METRONIDAZOLE ON BIOLOGICAL ACTION OF DOXORUBICIN

    Directory of Open Access Journals (Sweden)

    S. A. Yagubov

    2017-01-01

    Full Text Available Purpose. Investigation of the effect of the Metronizatol on the biological effect of Doxirubicin.Materials and methods. The studies were performed in the CBA/Lac males and C57Bl/6 females mice grafted with melanoma B16 and mucinous ovarian cancer CaO‑1. Metronidazole and Doxorubicin were used in the work. The antitumor effect was assessed by tumor volume and inhibition of tumor growth.Results. The data obtained indicate that Metronidazole used in oncologic practice for the treatment and prevention of infectious complications, and as a radiosensitizer, can enhance the antitumor effect of Doxorubicin, but this effect is accompanied by a significant increase of the cytostatic toxicity. These effects are leveled by increasing the interval between injections of Metronidazole and Doxorubicin up to 4 hours.Conclusion. The enhancement of the antitumor activity of Doxorubicin under the influence of Metronidazole depends on the interval between the administration of these drugs. When Metronidazole is used in cancer patients, the possibility of enhancing the toxic effect of cytostatics should be considered when they are simultaneously exposed. Patients receiving chemotherapy should be administered antitumor drugs no earlier than 4 hours after exposure to Metronidazole. 

  11. Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death.

    Science.gov (United States)

    Movafegh, Bahareh; Jalal, Razieh; Mohammadi, Zobeideh; Aldaghi, Seyyede Araste

    2018-04-11

    Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide-acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicin-induced cell death. Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24 h combined treatment of cells with doxorubicin (0.5 μM) and poly-L-arginine (1 μg ml-1) caused a small increase in doxorubicin-induced apoptosis and significant elevated necrosis in DU145 cells as compared to each agent alone. Conlusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferation-inducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Fluorescence spectroscopic studies on substituted porphyrins in homogeneous solvents and cationic micellar medium

    International Nuclear Information System (INIS)

    Phukan, Smritakshi; Mishra, Bhupendra; Chandra Shekar, K.P.; Kumar, Anil; Kumar, Dalip; Mitra, Sivaprasad

    2013-01-01

    Steady state and time-resolved fluorescence properties of porphyrin appended 1,3,4-oxadiazoles and thiazoles were described in homogeneous medium as well as in presence of cationic surfactant cetyltrimethylammonium bromide (CTAB). The electron withdrawing substituent on the porphyrin moiety in both the cases make a donor–spacer–acceptor type of intramolecular photoinduced electron transfer (PET) system resulting substantial quenching in porphyrin fluorescence due to partial energy migration towards the acceptor in the excited state. The increase in fluorescence yield as well as appreciable difference in fluorescence decay behavior in aqueous buffer solution of pH 4.2 from that in chloroform solution is believed due to partial protonation of the porphyrin ring. All the investigated systems show preferential binding into the interfacial region of the micellar sub-domain with varying degree of penetration depending on the nature of the substituent. Almost 2–4 fold increase in fluorescence yield for the probes is explained on the basis of restricted flexibility and corresponding decrease in total nonradiative rate inside the micellar interface layer. - Highlights: ► Synthesis and detail fluorescence studies of a series of porphyrin appended 1,3,4-oxadiazoles and thiazoles. ► Comparison of homogeneous solvent study with that in CTAB. ► Substantial porphyrin fluorescence quenching in donor–spacer–acceptor type system. ► Preferential binding of the substituted porphyrins in micellar sub-domain. ► Appreciable increase in fluorescence yield in micellar interface layer is due to decrease in total nonradiative rate.

  13. Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use.

    Science.gov (United States)

    Baxter-Holland, Mia; Dass, Crispin R

    2018-03-01

    The use of doxorubicin, an antineoplastic medication used for the treatment of cancers via mechanisms that prevent replication of cells or lead to their death, can result in damage to healthy cells as well as malignant. Among the affected cells are mesenchymal stem cells (MSCs), which are involved in the maintenance and repair of tissues in the body. This review explores the mechanisms of biological effects and damage attributed to doxorubicin on MSCs. The PubMed database was used as a source of literature for this review. Doxorubicin has the potential to lead to significant and irreversible damage to the human bone marrow environment, including MSCs. The primary known mechanism of these changes is through free radical damage and activation of apoptotic pathways. The presence of MSCs in culture or in vivo appears to either suppress or promote tumour growth. Interactions between doxorubicin and MSCs have the potential to increase chemotherapy resistance. Doxorubicin-induced damage to MSCs is of concern clinically. However, MSCs also have been associated with resistance of tumour cells to drugs including doxorubicin. Further studies, particularly in vivo, are needed to provide consistent results of how the doxorubicin-induced changes to MSCs affect treatment and patient health. © 2018 Royal Pharmaceutical Society.

  14. Direct interaction between verapamil and doxorubicin causes the lack of reversal effect of verapamil on P-glycoprotein mediated resistance to doxorubicin in vitro using L1210/VCR cells

    International Nuclear Information System (INIS)

    Breier, A.; Drobna, Z.; Barancik, M.

    1998-01-01

    Mouse leukemic cell sub-line L 1210/VCR exerts expressive multidrug resistance (MDR) that is mediated by P-glycoprotein. Cells originally adapted to vincristine are also extremely resistant to doxorubicin. Resistance to both vincristine and doxorubicin is connected with depression of drug uptake. While resistance of L 121 O cells to vincristine could be reversed by verapamil as chemo-sensitizer, resistance of cells to doxorubicin was insensitive to verapamil. Action of verapamil (well-known inhibitor of PGP activity) on multidrug resistance was often used as evidence that MDR is mediated by PGP. From this point it may be possible that the resistance of L1210/VCR cells to vincristine is mediated by PGP and the resistance to doxorubicin is mediated by other PGP-independent system. Another and more probable explanation of different effect of verapamil on resistance of L1210/VCR cells to vincristine and doxorubicin may be deduced from the following fact: Using UV spectroscopy we found that doxorubicin dissolved in water buffered medium interacts effectively with verapamil. This interaction may be responsible for the decrease of concentration of both drugs in free effective form and consequently for higher survival of cells. In contrast to doxorubicin vincristine does not give any interaction with verapamil that is measurable by UV spectroscopy and resistance of L1210/VCR cells to vincristine may be fully reversed by verapamil. (authors)

  15. A simplified radiometabolite analysis procedure for PET radioligands using a solid phase extraction with micellar medium

    International Nuclear Information System (INIS)

    Nakao, Ryuji; Halldin, Christer

    2013-01-01

    A solid phase extraction method has been developed for simple and high-speed direct determination of PET radioligands in plasma. Methods: This methodology makes use of a micellar medium and a solid-phase extraction cartridge for displacement of plasma protein bound radioligand and separation of PET radioligands from their radiometabolites without significant preparation. The plasma samples taken from monkey or human during PET measurements were mixed with a micellar eluent containing an anionic surfactant sodium dodecyl sulphate and loaded onto SPE cartridges. The amount of radioactivity corresponding to parent radioligand (retained on the cartridge) and its radioactive metabolites (eluted with micellar eluent) was measured. Results: Under the optimized conditions, excellent separation of target PET radioligands from their radiometabolites was achieved with a single elution and short run-time of 1 min. This method was successfully applied to study the metabolism for 11 C-labelled radioligands in human or monkey plasma. The amount of parent PET radioligands estimated by micellar solid phase extraction strongly corresponded with that determined by radio-LC. The improved throughput permitted the analysis of a large number of plasma samples (up to 13 samples per one PET study) for accurate estimation of metabolite-corrected input function during quantitative PET imaging studies. Conclusion: Solid phase extraction together with micellar medium is fast, sensitive and easy to use, and therefore it is an attractive alternative method to determine relative composition of PET radioligands in plasma

  16. Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

    Directory of Open Access Journals (Sweden)

    Gao W

    2017-02-01

    Full Text Available Wei Gao,1 Guihua Ye,1 Xiaochuan Duan,1 Xiaoying Yang,1 Victor C Yang1,2 1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics, School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA Abstract: The emergence of drug resistance is partially associated with overproduction of transferrin receptor (TfR. To overcome multidrug resistance (MDR and achieve tumor target delivery, we designed a novel biodegradable pH-sensitive micellar system modified with HAIYPRH, a TfR ligand (7pep. First, the polymers poly(l-histidine-coupled polyethylene glycol-2000 (PHIS-PEG2000 and 7pep-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (7pep-DSPE-PEG2000 were synthesized, and the mixed micelles were prepared by blending of PHIS-PEG2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2000 or 7pep-DSPE-PEG2000 (7-pep HD micelles. The micelles exhibited good size uniformity, high encapsulation efficiency, and a low critical micelle concentration. By changing the polymer ratio in the micellar formulation, the pH response range was specially tailored to pH ~6.0. When loaded with antitumor drug doxorubicin (DOX, the micelle showed an acid pH-triggering drug release profile. The cellular uptake and cytotoxicity study demonstrated that 7-pep HD micelles could significantly enhance the intracellular level and antitumor efficacy of DOX in multidrug-resistant cells (MCF-7/Adr, which attributed to the synergistic effect of poly(l-histidine-triggered endolysosom escape and TfR-mediated endocytosis. Most importantly, the in vivo imaging study confirmed the targetability of 7-pep HD micelles to MDR tumor. These findings indicated that 7-pep HD micelles would be a promising drug delivery system in the treatment of drug

  17. Direct effects of doxorubicin on skeletal muscle contribute to fatigue

    NARCIS (Netherlands)

    Norren, van K.; Helvoort, van A.; Argiles, J.M.; Tuijl, van S.; Arts, K.; Gorselink, M.; Laviano, A.; Kegler, D.; Haagsman, H.P.; Beek, E.M.

    2009-01-01

    Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation

  18. Synergistic Effect of Endogenous and Exogenous Aldehydes on Doxorubicin Toxicity in Yeast

    Directory of Open Access Journals (Sweden)

    Jana S. Miles

    2018-01-01

    Full Text Available Anthracyclines are frequently used to treat many cancers including triple negative breast cancer, which is commonly observed in African-American women (AA, and tend to be more aggressive, carry worse prognoses, and are harder to manage because they lack molecular targets. Although effective, anthracyclines use can be limited by serious side effects and eventually the development of drug resistance. In S. cerevisiae, mutants of HOM6 display hypersensitivity to doxorubicin. HOM6 is required for synthesis of threonine and interruption of the pathway leads to accumulation of the threonine intermediate L-aspartate-semialdehyde. This intermediate may synergize with doxorubicin to kill the cell. In fact, deleting HOM3 in the first step, preventing the pathway to reach the HOM6 step, rescues the sensitivity of the hom6 strain to doxorubicin. Using several S. cerevisiae strains (wild type, hom6, hom3, hom3hom6, ydj1, siz1, and msh2, we determined their sensitivity to aldehydes and to their combination with doxorubicin, cisplatin, and etoposide. Combination of formaldehyde and doxorubicin was most effective at reducing cell survival by 31-fold–39-fold (in wild type cells relative to doxorubicin and formaldehyde alone. This effect was dose dependent on doxorubicin. Cotreatment with formaldehyde and doxorubicin also showed increased toxicity in anthracycline-resistant strains siz1 and msh2. The hom6 mutant also showed sensitivity to menadione with a 2.5-fold reduction in cell survival. The potential use of a combination of aldehydes and cytotoxic drugs could potentially lead to applications intended to enhance anthracycline-based therapy.

  19. Energy transfer from triplet aromatic hydrocarbons to Tb3+ and Eu3+ in aqueous micellar solutions

    International Nuclear Information System (INIS)

    Almgren, M.; Grieser, F.; Thomas, J.K.

    1979-01-01

    The sensitization of Tb 3+ and Eu 3+ luminescence by energy transfer from aromatic triplet donors like naphthalene, bromonaphthalene, biphenyl, and phenanthrene in micellar sodium lauryl sulfate solution has been studied. Formal second-order rate constants for the energy transfer process in the micellar solutions were determined as 5 x 10 5 and 1.8 x 10 5 M -1 S -1 for transfer from biphenyl to Tb 3+ . The method of converting these rate constants to second-order constants pertaining to the micellar microenvironment is discussed; it is estimated that the transfer process at the micelles is charaterized by rate constants about one order of magnitude smaller than the formal ones. The transfer process is thus extremely slow. 7 figures

  20. Molecularly imprinted fluorescent probe based on FRET for selective and sensitive detection of doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhifeng, E-mail: 897061147@qq.com [College of Chemistry and Materials Science, Hengyang Normal University, Key Laboratory of Functional Organometallic Materials of Hunan Province University, Hengyang 421008 (China); Deng, Peihong; Li, Junhua [College of Chemistry and Materials Science, Hengyang Normal University, Key Laboratory of Functional Organometallic Materials of Hunan Province University, Hengyang 421008 (China); Xu, Li [Department of Applied Chemistry, College of Materials and Energy, South China Agricultural University, Guangzhou 510642 (China); Tang, Siping [College of Chemistry and Materials Science, Hengyang Normal University, Key Laboratory of Functional Organometallic Materials of Hunan Province University, Hengyang 421008 (China)

    2017-04-15

    Highlights: • FRET-based molecularly imprinted probe for detection of doxorubicin was prepared. • The detection limit of the probe was 13.8 nM for doxorubicin. • The FRET-based probe had a higher selectivity for the template than ordinary MIMs. - Abstract: In this work, a new type of fluorescent probe for detection of doxorubicin has been constructed by the combined use of fluorescence resonance energy transfer (FRET) technology and molecular imprinting technique (MIT). Using doxorubicin as the template, the molecularly imprinted polymer thin layer was fabricated on the surfaces of carbon dot (CD) modified silica by sol-gel polymerization. The excitation energy of the fluorescent donor (CDs) could be transferred to the fluorescent acceptor (doxorubicin). The FRET based fluorescent probe demonstrated high sensitivity and selectivity for doxorubicin. The detection limit was 13.8 nM. The fluorescent probe was successfully applied for detecting doxorubicin in doxorubicin-spiked plasmas with a recovery of 96.8–103.8%, a relative standard deviation (RSD) of 1.3–2.8%. The strategy for construction of FRET-based molecularly imprinted materials developed in this work is very promising for analytical applications.

  1. Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Reenu Punia

    Full Text Available Anthracyclines are efficient and potent agents to treat broad range of cancers but cytotoxicity induced by them limits their use in therapeutics. Use of plant-derived agents help to prevent or delay the process of cancer progression and their combination increases the anti-cancer potential of mainstream compound. However, multidrug resistance is major cause of treatment failure in cancer patients.In this study, combination treatments of fisetin or acacetin with doxorubicin were explored for their potential synergistic effect on non-small-cell lung carcinoma (NSCLC cells.During this study, NSCLC model cell lines A549 and H1299 were used to determine the combinatorial effect of phytochemicals namly acacetin and fisetin with doxorubicin.The effects of individual compounds and their combination on cell viability, clonogenic potential and cell cycle progression were studied. Efflux of doxorubicin was measured by spectrofluorophotometer, whereas accumulation inside the cells was analyzed by flow cytometry and confocal microscopy. Expression of MDR1 was checked by semi-quantitative PCR.The results showed that the cell viability of A549 and H1299 cells were significantly decreased in time- and dose-dependent manner, although A549 cells showed more sensitivity toward doxorubicin than H1299 cells. Mostly, combination of doxorubicin showed good synergy with acacetin in both the cell lines whereas, fisetin exerted synergistic effect only at 72 h of treatment in H1299 cells. Acacetin with doxorubicin caused G2/M arrest by downregulating CDK-cyclin complex in A549 cells. Acacetin-doxorubicin combination decreased the clonogenic potential of A549 and H1299 cells upto 82% and 59%, respectively, as compared to control. Acacetin also decreased efflux of doxorubicin by 59% after 30 mins of exposure to A549 cells and further increased accumulation of doxorubicin inside the cells upto 55% in 2 h. The modulatory effect of acacetin-doxorubicin combination on

  2. Complementary experimental-simulational study of surfactant micellar phase in the extraction process of metallic ions: Effects of temperature and salt concentration

    Science.gov (United States)

    Soto-Ángeles, Alan Gustavo; Rodríguez-Hidalgo, María del Rosario; Soto-Figueroa, César; Vicente, Luis

    2018-02-01

    The thermoresponsive micellar phase behaviour that exhibits the Triton-X-100 micelles by temperature effect and addition of salt in the extraction process of metallic ions was explored from mesoscopic and experimental points. In the theoretical study, we analyse the formation of Triton-X-100 micelles, load and stabilization of dithizone molecules and metallic ions extraction inside the micellar core at room temperature; finally, a thermal analysis is presented. In the experimental study, the spectrophotometric outcomes confirm the solubility of the copper-dithizone complex in the micellar core, as well as the extraction of metallic ions of aqueous environment via a cloud-point at 332.2 K. The micellar solutions with salt present a low absorbance value compared with the micellar solutions without salt. The decrease in the absorbance value is attributed to a change in the size of hydrophobic region of colloidal micelles. All transitory stages of extraction process are discussed and analysed in this document.

  3. Ultrafast relaxation dynamics of a biologically relevant probe dansyl at the micellar surface.

    Science.gov (United States)

    Sarkar, Rupa; Ghosh, Manoranjan; Pal, Samir Kumar

    2005-02-01

    We report picosecond-resolved measurement of the fluorescence of a well-known biologically relevant probe, dansyl chromophore at the surface of a cationic micelle (cetyltrimethylammonium bromide, CTAB). The dansyl chromophore has environmentally sensitive fluorescence quantum yields and emission maxima, along with large Stokes shift. In order to study the solvation dynamics of the micellar environment, we measured the fluorescence of dansyl chromophore attached to the micellar surface. The fluorescence transients were observed to decay (with time constant approximately 350 ps) in the blue end and rise with similar timescale in the red end, indicative of solvation dynamics of the environment. The solvation correlation function is measured to decay with time constant 338 ps, which is much slower than that of ordinary bulk water. Time-resolved anisotropy of the dansyl chromophore shows a bi-exponential decay with time constants 413 ps (23%) and 1.3 ns (77%), which is considerably slower than that in free solvents revealing the rigidity of the dansyl-micelle complex. Time-resolved area-normalized emission spectroscopic (TRANES) analysis of the time dependent emission spectra of the dansyl chromophore in the micellar environment shows an isoemissive point at 21066 cm-1. This indicates the fluorescence of the chromophore contains emission from two kinds of excited states namely locally excited state (prior to charge transfer) and charge transfer state. The nature of the solvation dynamics in the micellar environments is therefore explored from the time-resolved anisotropy measurement coupled with the TRANES analysis of the fluorescence transients. The time scale of the solvation is important for the mechanism of molecular recognition.

  4. Abatement by Naringenin of Doxorubicin-Induced Cardiac Toxicity in Rats

    International Nuclear Information System (INIS)

    Arafa, H.M.; Abd-Ellah, M.F.; Hafez, H.F.

    2005-01-01

    Doxorubicin is one of the most active cytotoxic agents in current use. It has proven efficacy in various malignancies either alone or combined with other cytocidal agents. The clinical usefulness of the anthracycline drug has been precluded by cardiac toxicity. Many therapeutic interventions have been attempted to improve the therapeutic benefits of the drug. Few, however, have been efficacious in this setting. Purpose: We have addressed in the current study the possible protective effects of naringenin, a flavonoid known to have anti-oxidant properties, on doxorubicin induced cardiac toxicity in male Swiss albino rats. Methods: Forty male Swiss albino rats were used in this study. Naringenin (25 mg/kg body weight) was administered daily by gavage for 7 consecutive days before a cumulative single dose of doxorubicin (15 mg/kg body weight, ip). Doxorubicin induced marked biochemical alterations characteristic of cardiac toxicity including, elevated activities of serum total lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), enhanced lipid peroxidation measured as malonaldehyde (MDA). The anthracycline drug has also reduced the cardiac enzymatic activities of superoxide dismutase (SOD), glutathione-Stransferase (GST) and catalase (CAT). Besides, it reduced significantly the reduced glutathione (GSH) level, but it increased the total NO content in heart tissue. Prior administration of naringenin ahead of doxorubicin challenge ameliorated all these biochemical markers. Taken together, one could conclude that naringenin has a protective role in the abatement of doxorubicin-induced cardiac toxicity that resides, at least in part, on its anti-radical effects and regulatory role on NO production

  5. Multicompartment micellar aggregates of linear ABC amphiphiles in solvents selective for the C block: A Monte Carlo simulation

    KAUST Repository

    Zhu, Yutian

    2012-01-01

    In the current study, we applied the Monte Carlo method to study the self-assembly of linear ABC amphiphiles composed of two solvophobic A and B blocks and a solvophilic C block. A great number of multicompartment micelles are discovered from the simulations and the detailed phase diagrams for the ABC amphiphiles with different block lengths are obtained. The simulation results reveal that the micellar structure is largely controlled by block length, solvent quality, and incompatibility between the different block types. When the B block is longer than or as same as the terminal A block, a rich variety of micellar structures can be formed from ABC amphiphiles. By adjusting the solvent quality or incompatibility between the different block types, multiple morphological transitions are observed. These morphological sequences are well explained and consistent with all the previous experimental and theoretical studies. Despite the complexity of the micellar structures and morphological transitions observed for the self-assembly of ABC amphiphiles, two important common features of the phase behavior are obtained. In general, the micellar structures obtained in the current study can be divided into zero-dimensional (sphere-like structures, including bumpy-surfaced spheres and sphere-on-sphere structures), one-dimensional (cylinder-like structures, including rod and ring structures), two-dimensional (layer-like structures, including disk, lamella and worm-like and hamburger structures) and three-dimensional (vesicle) structures. It is found that the micellar structures transform from low- to high- dimensional structures when the solvent quality for the solvophobic blocks is decreased. In contrast, the micellar structures transform from high- to low-dimensional structures as the incompatibility between different block types increases. Furthermore, several novel micellar structures, such as the CBABC five-layer vesicle, hamburger, CBA three-layer ring, wormlike shape with

  6. Infusion cisternography

    International Nuclear Information System (INIS)

    Magnaes, B.; Rootwelt, K.; Sjaastad, O.

    1976-01-01

    A source of error in cerebrospinal fluid (CSF) infusion tests is leakage at the dural puncture site. The addition of a bolus of radionuclide to the infusion fluid was helpful in detecting the existence of leakage as shown by increased infusion pressure in six of eight patients studied with and without scintigraphic evidence of leakage. Comparison of CSF dynamics in 26 patients studied by infusion cisternography and conventional cisternography showed similar patterns, suggesting no alteration of CSF dynamics by the artificial CSF infusion. Combining the two tests, therefore, resulted in simple identification of the leakage and saved the patient time and discomfort

  7. Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes.

    Science.gov (United States)

    Ververis, Katherine; Rodd, Annabelle L; Tang, Michelle M; El-Osta, Assam; Karagiannis, Tom C

    2011-12-01

    Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.

  8. Phenotyping and Visualizing Infusion-Related Reactions for Breast Cancer Patients

    Science.gov (United States)

    Sun, Deyu; Sarda, Gopal; Skube, Steven J.; Blaes, Anne H.; Khairat, Saif; Melton, Genevieve B.; Zhang, Rui

    2018-01-01

    Infusion-related reactions (IRRs) are typical adverse events for breast cancer patients. Detecting IRRs and visualizing their occurance associated with the drug treatment would potentially assist clinicians to improve patient safety and help researchers model IRRs and analyze their risk factors. We developed and evaluated a phenotyping algorithm to detect IRRs for breast cancer patients. We also designed a visualization prototype to render IRR patients’ medications, lab tests and vital signs over time. By comparing with the 42 randomly selected doses that are manually labeled by a domain expert, the sensitivity, positive predictive value, specificity, and negative predictive value of the algorithms are 69%, 60%, 79%, and 85%, respectively. Using the algorithm, an incidence of 6.4% of patients and 1.8% of doses for docetaxel, 8.7% and 3.2% for doxorubicin, 10.4% and 1.2% for paclitaxel, 16.1% and 1.1% for trastuzumab were identified retrospectively. The incidences estimated are consistent with related studies. PMID:29295166

  9. Optimization of doxorubicin loading for superabsorbent polymer microspheres: in vitro analysis.

    Science.gov (United States)

    Liu, David M; Kos, Sebastian; Buczkowski, Andrzej; Kee, Stephen; Munk, Peter L; Klass, Darren; Wasan, Ellen

    2012-04-01

    This study was designed to establish the ability of super-absorbent polymer microspheres (SAP) to actively uptake doxorubicin and to establish the proof of principle of SAP's ability to phase transfer doxorubicin onto the polymer matrix and to elute into buffer with a loading method that optimizes physical handling and elution characteristics. Phase I: 50-100 μm SAP subject to various prehydration methods (normal saline 10 cc, hypertonic saline 4 cc, iodinated contrast 10 cc) or left in their dry state, and combined with 50 mg of clinical grade lyophilized doxorubicin reconstituted with various methods (normal saline 10 cc and 25 cc, sterile water 4 cc, iodinated contrast 5 cc) were placed in buffer and assessed based on loading, handling, and elution utilizing high-performance liquid chromatography (HPLC). Phase II: top two performing methods were subject to loading of doxorubicin (50, 75, 100 mg) in a single bolus (group A) or as a serial loading method (group B) followed by measurement of loading vs. time and elution vs. time. Phase I revealed the most effective loading mechanisms and easiest handling to be dry (group A) vs. normal saline prehydrated (group B) SAP with normal saline reconstituted doxorubicin (10 mg/mL) with loading efficiencies of 83.1% and 88.4%. Phase II results revealed unstable behavior of SAP with 100 mg of doxorubicin and similar loading/elution profiles of dry and prehydrated SAP, with superior handling characteristics of group B SAP at 50 and 75 mg. SAP demonstrates the ability to load and bulk phase transfer doxorubicin at 50 and 75 mg with ease of handling and optimal efficiency through dry loading of SAP.

  10. Interaction of antihypertensive drug amiloride with metal ions in micellar medium using fluorescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Gujar, Varsha; Pundge, Vijaykumar; Ottoor, Divya, E-mail: divya@chem.unipune.ac.in

    2015-05-15

    Steady state and life time fluorescence spectroscopy have been employed to study the interaction of antihypertensive drug amiloride with biologically important metal ions i.e. Cu{sup 2+}, Fe{sup 2+}, Ni{sup 2+} and Zn{sup 2+} in various micellar media (anionic SDS (sodium dodecyl sulfate), nonionic TX-100 (triton X-100) and cationic CTAB (cetyl trimethyl ammonium bromide)). It was observed that fluorescence properties of drug remain unaltered in the absence of micellar media with increasing concentration of metal ions. However, addition of Cu{sup 2+}, Fe{sup 2+} and Ni{sup 2+} caused fluorescence quenching of amiloride in the presence of anionic micelle, SDS. Binding of drug with metal ions at the charged micellar interface could be the possible reason for this pH-dependent metal-mediated fluorescence quenching. There were no remarkable changes observed due to metal ions addition when drug was present in cationic and nonionic micellar medium. The binding constant and bimolecular quenching constant were evaluated and compared for the drug–metal complexes using Stern–Volmer equation and fluorescence lifetime values. - Highlights: • Interaction of amiloride with biologically important metal ions, Fe{sup 2+}, Cu{sup 2+}, Ni{sup 2+} and Zn{sup 2+}. • Monitoring the interaction in various micelle at different pH by fluorescence spectroscopy. • Micelles acts as receptor, amiloride as transducer and metal ions as analyte in the present system. • Interaction study provides pH dependent quenching and binding mechanism of drug with metal ions.

  11. Interaction of antihypertensive drug amiloride with metal ions in micellar medium using fluorescence spectroscopy

    International Nuclear Information System (INIS)

    Gujar, Varsha; Pundge, Vijaykumar; Ottoor, Divya

    2015-01-01

    Steady state and life time fluorescence spectroscopy have been employed to study the interaction of antihypertensive drug amiloride with biologically important metal ions i.e. Cu 2+ , Fe 2+ , Ni 2+ and Zn 2+ in various micellar media (anionic SDS (sodium dodecyl sulfate), nonionic TX-100 (triton X-100) and cationic CTAB (cetyl trimethyl ammonium bromide)). It was observed that fluorescence properties of drug remain unaltered in the absence of micellar media with increasing concentration of metal ions. However, addition of Cu 2+ , Fe 2+ and Ni 2+ caused fluorescence quenching of amiloride in the presence of anionic micelle, SDS. Binding of drug with metal ions at the charged micellar interface could be the possible reason for this pH-dependent metal-mediated fluorescence quenching. There were no remarkable changes observed due to metal ions addition when drug was present in cationic and nonionic micellar medium. The binding constant and bimolecular quenching constant were evaluated and compared for the drug–metal complexes using Stern–Volmer equation and fluorescence lifetime values. - Highlights: • Interaction of amiloride with biologically important metal ions, Fe 2+ , Cu 2+ , Ni 2+ and Zn 2+ . • Monitoring the interaction in various micelle at different pH by fluorescence spectroscopy. • Micelles acts as receptor, amiloride as transducer and metal ions as analyte in the present system. • Interaction study provides pH dependent quenching and binding mechanism of drug with metal ions

  12. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity

    International Nuclear Information System (INIS)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O.; Lücker, Petra B.; Zandstra, Peter W.; Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V.; Wickham, Thomas J.

    2012-01-01

    Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. -- Highlights: ► Novel approach using stem cell-derived cardiomyocytes to assess preclinical safety. ► HER2-targeted liposomal doxorubicin has improved safety profile vs free doxorubicin

  13. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Lücker, Petra B.; Zandstra, Peter W. [University of Toronto, 160 College Street, Office 1116, Toronto, Ontario M5S 3E1 (Canada); Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Wickham, Thomas J., E-mail: twickham@merrimackpharma.com [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States)

    2012-07-01

    Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. -- Highlights: ► Novel approach using stem cell-derived cardiomyocytes to assess preclinical safety. ► HER2-targeted liposomal doxorubicin has improved safety profile vs free doxorubicin

  14. Echocardiographic changes in dogs long term treated with doxorubicin

    International Nuclear Information System (INIS)

    Silva, C.E.V.

    2005-01-01

    The doxorubicin's cardiotoxity was evaluated in seven clinically healthy adult dogs by means of intravenously injections of 30 mg/m2 of doxorubicin chloridate (Adriblastina), every 21 days, for 168 days (group A), performing a total cumulative dose of 240 mg/m2. Seven other dogs received 5 ml of 0.9% saline sterile solution intravenously (group B), following the protocol described above

  15. Molecular organization and dynamics of micellar phase of polyelectrolyte-surfactant complexes: ESR spin probe study

    Science.gov (United States)

    Wasserman, A. M.; Kasaikin, V. A.; Zakharova, Yu. A.; Aliev, I. I.; Baranovsky, V. Yu.; Doseva, V.; Yasina, L. L.

    2002-04-01

    Molecular dynamics and organization of the micellar phase of complexes of linear polyelectrolytes with ionogenic and non-ionogenic surfactants was studied by the ESR spin probe method. Complexes of polyacrylic acid (PAA) and sodium polystyrenesulfonate (PSS) with alkyltrimethylammonium bromides (ATAB), as well as complexes of poly- N, N'-dimethyldiallylammonium chloride (PDACL) with sodium dodecylsulfate (SDS) were studied. The micellar phase of such complexes is highly organized molecular system, molecular ordering of which near the polymeric chain is much higher than in the 'center' of the micelle, it depends on the polymer-detergent interaction, flexibility of polymeric chain and length of carbonic part of the detergent molecule. Complexes of polymethacrylic acid (PMAA) with non-ionic detergent (dodecyl-substituted polyethyleneglycol), show that the local mobility of surfactant in such complexes is significantly lower than in 'free' micelles and depends on the number of micellar particles participating in formation of complexes.

  16. A Novel Submicron Emulsion System Loaded with Doxorubicin Overcome Multi-Drug Resistance in MCF-7/ADR Cells.

    Science.gov (United States)

    Zhou, W P; Hua, H Y; Sun, P C; Zhao, Y X

    2015-01-01

    The purpose of the present study was to develop the Solutol HS15-based doxorubicin submicron emulsion with good stability and overcoming multi-drug resistance. In this study, we prepared doxorubicin submicron emulsion, and examined the stability after autoclaving, the in vitro cytotoxic activity, the intracellular accumulation and apoptpsis of doxorubicin submicron emulsion in MCF-7/ADR cells. The physicochemical properties of doxorubicin submicron emulsion were not significantly affected after autoclaving. The doxorubicin submicron emulsion significantly increased the intracellular accumulation of doxorubicin submicron emulsion and enhanced cytotoxic activity and apoptotic effects of doxorubicin. These results may be correlated to doxorubicin submicron emulsion inhibitory effects on efflux pumps through the progressive release of intracellular free Solutol HS15 from doxorubicin submicron emulsion. Furthermore, these in vitro results suggest that the Solutol HS15-based submicron emulsion may be a potentially useful drug delivery system to circumvent multi-drug resistance of tumor cells.

  17. Chemomodulation of Doxorubicin Pharmacodynamics

    Science.gov (United States)

    2002-10-01

    doxorubicin in athymic nude mice with multidrug resistant MCF-7 human tumor xenografts. High pressure liquid chromatography ( HPLC ) will be utilized to measure...is a flavonoid that causes 50% growth tumor growth support by the host (42). The clinical efficacy of inhibition of tumor cells at 60 nM (57). It also

  18. Infusion Extractor

    Science.gov (United States)

    Chang-Diaz, Franklin R.

    1988-01-01

    Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

  19. Optimization of Doxorubicin Loading for Superabsorbent Polymer Microspheres: in vitro Analysis

    International Nuclear Information System (INIS)

    Liu, David M.; Kos, Sebastian; Buczkowski, Andrzej; Kee, Stephen; Munk, Peter L.; Klass, Darren; Wasan, Ellen

    2012-01-01

    Purpose: This study was designed to establish the ability of super-absorbent polymer microspheres (SAP) to actively uptake doxorubicin and to establish the proof of principle of SAP’s ability to phase transfer doxorubicin onto the polymer matrix and to elute into buffer with a loading method that optimizes physical handling and elution characteristics. Methods: Phase I: 50–100 μm SAP subject to various prehydration methods (normal saline 10 cc, hypertonic saline 4 cc, iodinated contrast 10 cc) or left in their dry state, and combined with 50 mg of clinical grade lyophilized doxorubicin reconstituted with various methods (normal saline 10 cc and 25 cc, sterile water 4 cc, iodinated contrast 5 cc) were placed in buffer and assessed based on loading, handling, and elution utilizing high-performance liquid chromatography (HPLC). Phase II: top two performing methods were subject to loading of doxorubicin (50, 75, 100 mg) in a single bolus (group A) or as a serial loading method (group B) followed by measurement of loading vs. time and elution vs. time. Results: Phase I revealed the most effective loading mechanisms and easiest handling to be dry (group A) vs. normal saline prehydrated (group B) SAP with normal saline reconstituted doxorubicin (10 mg/mL) with loading efficiencies of 83.1% and 88.4%. Phase II results revealed unstable behavior of SAP with 100 mg of doxorubicin and similar loading/elution profiles of dry and prehydrated SAP, with superior handling characteristics of group B SAP at 50 and 75 mg. Conclusions: SAP demonstrates the ability to load and bulk phase transfer doxorubicin at 50 and 75 mg with ease of handling and optimal efficiency through dry loading of SAP.

  20. Vertical structures in vibrated wormlike micellar solutions

    Science.gov (United States)

    Epstein, Tamir; Deegan, Robert

    2008-11-01

    Vertically vibrated shear thickening particulate suspensions can support a free-standing interfaces oriented parallel to gravity. We find that shear thickening worm-like micellar solutions also support such vertical interfaces. Above a threshold in acceleration, the solution spontaneously accumulates into a labyrinthine pattern characterized by a well-defined vertical edge. The formation of vertical structures is of interest because they are unique to shear-thickening fluids, and they indicate the existence of an unknown stress bearing mechanism.

  1. Multiscale Modeling of the Effects of Salt and Perfume Raw Materials on the Rheological Properties of Commercial Threadlike Micellar Solutions.

    Science.gov (United States)

    Tang, Xueming; Zou, Weizhong; Koenig, Peter H; McConaughy, Shawn D; Weaver, Mike R; Eike, David M; Schmidt, Michael J; Larson, Ronald G

    2017-03-23

    We link micellar structures to their rheological properties for two surfactant body-wash formulations at various concentrations of salts and perfume raw materials (PRMs) using molecular simulations and micellar-scale modeling, as well as traditional surfactant packing arguments. The two body washes, namely, BW-1EO and BW-3EO, are composed of sodium lauryl ethylene glycol ether sulfate (SLEnS, where n is the average number of ethylene glycol repeat units), cocamidopropyl betaine (CAPB), ACCORD (which is a mixture of six PRMs), and NaCl salt. BW-3EO is an SLE3S-based body wash, whereas BW-1EO is an SLE1S-based body wash. Additional PRMs are also added into the body washes. The effects of temperature, salt, and added PRMs on micellar lengths, breakage times, end-cap free energies, and other properties are obtained from fits of the rheological data to predictions of the "Pointer Algorithm" [ Zou , W. ; Larson , R.G. J. Rheol. 2014 , 58 , 1 - 41 ], which is a simulation method based on the Cates model of micellar dynamics. Changes in these micellar properties are interpreted using the Israelachvili surfactant packing argument. From coarse-grained molecular simulations, we infer how salt modifies the micellar properties by changing the packing between the surfactant head groups, with the micellar radius remaining nearly constant. PRMs do so by partitioning to different locations within the micelles according to their octanol/water partition coefficient P OW and chemical structures, adjusting the packing of the head and/or tail groups, and by changing the micelle radius, in the case of a large hydrophobic PRM. We find that relatively hydrophilic PRMs with log P OW 4, are isolated deep inside the micelle, separating from the tails and swelling the radius of the micelle, leading to shorter micelles and much lower viscosities, leading eventually to swollen-droplet micelles.

  2. Structural and phase transition changes of sodium dodecyl sulfate micellar solution in alcohols probed by small-angle neutron scattering (SANS)

    Energy Technology Data Exchange (ETDEWEB)

    Putra, Edy Giri Rachman [Neutron Scattering Laboratory, National Nuclear Energy Agency of Indonesia (BATAN), Gedung 40 BATAN, Kawasan Puspiptek Serpong, Tangerang 15314 (Indonesia); Patriati, Arum [Neutron Scattering Laboratory, National Nuclear Energy Agency of Indonesia (BATAN), Gedung 40 BATAN, Kawasan Puspiptek Serpong, Tangerang 15314 (Indonesia); Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Gadjah Mada, Bulaksumur, Yogyakarta 55281, Indonesia giri@batan.go.id (Indonesia)

    2015-04-16

    Small-angle neutron scattering (SANS) measurements on 0.3M sodium dodecyl sulfate (SDS) micellar solutions have been performed in the presence of n-alcohols, from ethanol to decanol at different alcohol concentrations, 2–10 wt%. The ellipsoid micellar structure which occurred in the 0.3M SDS in aqueous solution with the size range of 30–50 Å has different behavior at various hydrocarbon chain length and concentration of alcohols. At low concentration and short chain-length of alcohols, such as ethanol, propanol, and butanol, the size of micelles reduced and had a spherical-like structure. The opposite effect occurred as medium to long chain alcohols, such as hexanol, octanol and decanol was added into the 0.3M SDS micellar solutions. The micelles structure changed to be more elongated in major axis and then crossed the critical phase transition from micellar solution into liquid crystal phase as lamellar structure emerged by further addition of alcohols. The inter-lamellar distances were also depending on the hydrocarbon chain length and concentration of alcohols. In the meantime, the persistent micellar structures occurred in addition of medium chain of n-alcohol, pentanol at all concentrations.

  3. Structural and phase transition changes of sodium dodecyl sulfate micellar solution in alcohols probed by small-angle neutron scattering (SANS)

    International Nuclear Information System (INIS)

    Putra, Edy Giri Rachman; Patriati, Arum

    2015-01-01

    Small-angle neutron scattering (SANS) measurements on 0.3M sodium dodecyl sulfate (SDS) micellar solutions have been performed in the presence of n-alcohols, from ethanol to decanol at different alcohol concentrations, 2–10 wt%. The ellipsoid micellar structure which occurred in the 0.3M SDS in aqueous solution with the size range of 30–50 Å has different behavior at various hydrocarbon chain length and concentration of alcohols. At low concentration and short chain-length of alcohols, such as ethanol, propanol, and butanol, the size of micelles reduced and had a spherical-like structure. The opposite effect occurred as medium to long chain alcohols, such as hexanol, octanol and decanol was added into the 0.3M SDS micellar solutions. The micelles structure changed to be more elongated in major axis and then crossed the critical phase transition from micellar solution into liquid crystal phase as lamellar structure emerged by further addition of alcohols. The inter-lamellar distances were also depending on the hydrocarbon chain length and concentration of alcohols. In the meantime, the persistent micellar structures occurred in addition of medium chain of n-alcohol, pentanol at all concentrations

  4. Inhibition of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Feng [Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072 (China); Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yang, Yong, E-mail: yyang@houstonmethodist.org [Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Medicine, Weill Cornell Medical College, New York, NY 10065 (United States)

    2014-11-21

    Highlights: • Suppression of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin. • Repression of PKM2 affects the glycolysis and decreases ATP production. • Downregulation of PKM2 increases the intracellular accumulation of doxorubicin. • Inhibition of PKM2 enhances the antitumor efficacy of doxorubicin in vivo. - Abstract: Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, we examined the effects of combined treatment with doxorubicin and anti-PKM2 small interfering RNA (siRNA) on triple-negative breast cancer (TNBC). The suppression of PKM2 resulted in changes in glucose metabolism, leading to decreased synthesis of adenosine triphosphate (ATP). Reduced levels of ATP resulted in the intracellular accumulation of doxorubicin, consequently enhancing the therapeutic efficacy of this drug in several triple-negative breast cancer cell lines. Furthermore, the combined effect of PKM2 siRNA and doxorubicin was evaluated in an in vivo MDA-MB-231 orthotopic breast cancer model. The siRNA was systemically administered through a polyethylenimine (PEI)-based delivery system that has been extensively used. We demonstrate that the combination treatment showed superior anticancer efficacy as compared to doxorubicin alone. These findings suggest that targeting PKM2 can increase the efficacy of chemotherapy, potentially providing a new approach for improving the outcome of chemotherapy in patients with TNBC.

  5. Strip waves in vibrated shear-thickening wormlike micellar solutions

    Science.gov (United States)

    Epstein, T.; Deegan, R. D.

    2010-06-01

    We present an instability in vertically vibrated dilute wormlike micellar solutions. Above a critical driving acceleration the fluid forms elongated solitary domains of high amplitude waves. We model this instability using a Mathieu equation modified to account for the non-Newtonian character of the fluid. We find that our model successfully reproduces the observed transitions.

  6. Amplification of Chirality through Self-Replication of Micellar Aggregates in Water

    KAUST Repository

    Bukhriakov, Konstantin; Almahdali, Sarah; Rodionov, Valentin

    2015-01-01

    We describe a system in which the self-replication of micellar aggregates results in a spontaneous amplification of chirality in the reaction products. In this system, amphiphiles are synthesized from two "clickable" fragments: a water-soluble "head

  7. Transepithelial Transport of Curcumin in Caco-2 Cells Is significantly Enhanced by Micellar Solubilisation.

    Science.gov (United States)

    Frank, Jan; Schiborr, Christina; Kocher, Alexa; Meins, Jürgen; Behnam, Dariush; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

    2017-03-01

    Curcumin, the active constituent of Curcuma longa L. (family Zingiberaceae), has gained increasing interest because of its anti-cancer, anti-inflammatory, anti-diabetic, and anti-rheumatic properties associated with good tolerability and safety up to very high doses of 12 g. Nanoscaled micellar formulations on the base of Tween 80 represent a promising strategy to overcome its low oral bioavailability. We therefore aimed to investigate the uptake and transepithelial transport of native curcumin (CUR) vs. a nanoscaled micellar formulation (Sol-CUR) in a Caco-2 cell model. Sol-CUR afforded a higher flux than CUR (39.23 vs. 4.98 μg min -1  cm -2 , respectively). This resulted in a higher P app value of 2.11 × 10 -6  cm/s for Sol-CUR compared to a P app value of 0.56 × 10 -6  cm/s for CUR. Accordingly a nearly 9.5 fold higher amount of curcumin was detected on the basolateral side at the end of the transport experiments after 180 min with Sol-CUR compared to CUR. The determined 3.8-fold improvement in the permeability of curcumin is in agreement with an up to 185-fold increase in the AUC of curcumin observed in humans following the oral administration of the nanoscaled micellar formulation compared to native curcumin. The present study demonstrates that the enhanced oral bioavailability of micellar curcumin formulations is likely a result of enhanced absorption into and increased transport through small intestinal epithelial cells.

  8. Micellar enhanced spectrofluorimetric methods: application to the determination of pyrene

    Energy Technology Data Exchange (ETDEWEB)

    Singh, H.; Hinze, W.L.

    1982-01-01

    The effects of cationic hexadecyltrimethylammonium chloride (CTAC), nonionic polyoxyethylene(9.5)p-1,1,3,3-tetramethylbutylphenol, Triton X-100 (TX-100), and anionic sodium dodecylsulfate (NaLS) surfactant micelles upon the spectrofluorimetric determination of pyrene is described. It was found that the intensity of the pyrene fluorescence is enhanced from 3 to 16 times in the presence of the micellar systems. Possible reasons for this micellar induced enhanced fluorescence are discussed. The spectral parameters, fluorescence lifetimes, quantum yields, lower detection limits, and analytical figures of merit for pyrene in CTAC, NaLS, TX-100, ethanol, and water are compared. The detection limit of pyrene in the presence of micelles (approx. 1.0 x 10/sup -10/ M) is about an order of magnitude lower than that possible in alcohol alone. A brief discussion on the predicted general applicability of this new technique in fluorimetric analysis is also given. 4 figures, 2 tables.

  9. αvβ3 integrin-targeted micellar mertansine prodrug effectively inhibits triple-negative breast cancer in vivo

    Directory of Open Access Journals (Sweden)

    Zhong P

    2017-10-01

    Full Text Available Ping Zhong,1,2 Xiaolei Gu,1,2 Ru Cheng,1,2 Chao Deng,1,2 Fenghua Meng,1,2 Zhiyuan Zhong1,2 1Biomedical Polymers Laboratory, 2Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, China Abstract: Antibody-mertansine (DM1 conjugates (AMCs are among the very few active targeting therapeutics that are approved or clinically investigated for treating various cancers including metastatic breast cancer. However, none of the AMCs are effective for the treatment of triple-negative breast cancers (TNBCs. Here, we show that cRGD-decorated, redox-activatable micellar mertansine prodrug (cRGD-MMP can effectively target and deliver DM1 to αvβ3 integrin overexpressing MDA-MB-231 TNBC xenografts in nude mice, resulting in potent tumor growth inhibition. 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays showed that cRGD-MMP had obvious targetability to MDA-MB-231 cells with a low half-maximal inhibitory concentration (IC50 of 0.18 µM, which was close to that of free DM1 and 2.2-fold lower than that of micellar mertansine prodrug (MMP; nontargeting control. The confocal microscopy studies demonstrated that cRGD-MMP mediated a clearly more efficient cellular uptake and intracellular release of doxorubicin (used as a fluorescent anticancer drug model in MDA-MB-231 cells. Notably, cRGD-MMP loaded with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR; a hydrophobic near-infrared dye was shown to quickly accumulate in the MDA-MB-231 tumor with strong DiR fluorescence from 2 to 24 h post injection. MMP loaded with DiR could also accumulate in the tumor, although significantly less than cRGD-MMP. The biodistribution studies revealed a high DM1 accumulation of 8.1%ID/g in the tumor for cRGD-MMP at 12 h post injection. The therapeutic results demonstrated that cRGD-MMP effectively suppressed MDA-MB-231 tumor growth at

  10. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    Directory of Open Access Journals (Sweden)

    Ninna Aggerholm-Pedersen

    2016-01-01

    Full Text Available Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

  11. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy.

    Science.gov (United States)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal; Meldgaard, Peter; Kassem, Moustapha; Sandahl Sorensen, Boe

    2016-01-01

    Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

  12. A kinetic study of 1,3-dipolar cycloadditions in micellar media

    NARCIS (Netherlands)

    Rispens, T; Engberts, JBFN

    2003-01-01

    The kinetics of the 1,3-dipolar cycloadditions (DC) of benzonitrile oxide with a series of N-substituted maleimides in micellar media have been investigated. Surfactants studied include anionic sodium dodecyl sulfate, cationic cetyltrimethylammonium bromide, and a series of nonionic alkyl

  13. Preliminary results of multicenter phase II trial of docetaxel (Taxotere) in combination with doxorubicin as first line chemotherapy in Indonesian patients with advanced or metastatic breast cancer.

    Science.gov (United States)

    Muthalib, A; Darwis, I; Prayogo, N; Sutjipto

    2000-05-01

    Docetaxel and doxorubicin have produced a high degree of activity in previously untreated/treated patients with metastatic breast cancer (MBC). The efficacy of Taxotere (T) single agent as 2nd line chemotherapy is well established in large randomized phase III studies. The objective of this study is to confirm the efficacy and safety of a combination of Taxotere with doxorubicin as 1st line chemotherapy in Indonesian MBC patients. TREATMENT AND METHOD: Eighteen patients age < or = 70 years with advanced or metastatic breast cancer (MBC) with no prior taxane chemotherapy or prior cumulative doxorubicin (D) of no more than 250 mg/m2 and no heart disease were enrolled in this phase II study of D (50 mg/m2) IV bolus followed one hour later by Taxotere (T) 60 mg/m2 IV infusion over 1 hour every 3 weeks for 6 cycles treatments. A 3-day oral corticosteroid premedication was administered starting one day before the infusion of each cycle. Left ventricular ejection fraction (LVEF) was evaluated at baseline and after cycle 6. 18 patients (pts) have been treated with 108 cycles administered. Median age was 46 years (31-58), WHO PS 0 = 50%, 1 = 50% and number of organs involved were: 2 (72%), 3 (22%) and 4 (6%). After 3 cycles, partial (PR) and no change (NC) responses occurred in 15 pts (83.3%) and 3 pts (16.7%). The best overall response after 6 cycles, including complete (CR) and partial (PR) responses, occurred in 13 pts (72.2%) including 3 CRs and 10 PRs. Two patients with extensive liver metastases at the baseline had a complete disappearance after 6 cycles. No patients developed congestive heart failure (CHF). Grade 3/4 hematological toxicities included leukopenia in 18 pts (100%), febrile neutropenia in 6 pts (33%), leukopenia with infection in 2 pts (11%), leukopenia with fever in 1 pt (5.5%), and anemia in 6 pts (33.3%). Nonhematological toxicities grade 3/4 included alopecia (61%), asthenia (4.6%), nausea/vomiting (2.7%), pain (2.7%), stomatitis (2.7%), and

  14. Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

    Energy Technology Data Exchange (ETDEWEB)

    Gharanei, M.; Hussain, A. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Janneh, O. [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom); Pharmacology Research Laboratories, 70, Pembroke Place, The University of Liverpool, Liverpool. L69 3GF (United Kingdom); Maddock, H.L., E-mail: h.maddock@coventry.ac.uk [Department of Biomolecular and Sport Sciences, Coventry University, Cox Street, Coventry, CV1 5FB (United Kingdom)

    2013-04-15

    Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

  15. Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

    International Nuclear Information System (INIS)

    Gharanei, M.; Hussain, A.; Janneh, O.; Maddock, H.L.

    2013-01-01

    Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

  16. Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes

    OpenAIRE

    Karagiannis, Tom C; Lin, Ann JE; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

    2010-01-01

    Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubic...

  17. Schedule-dependency of doxorubicin and vinblastine in EAT tumours in mice

    International Nuclear Information System (INIS)

    Auersperg, M.; Pogacnik, A.; Kloboves-Prevodnik, V.; Sersa, G.; Cemazar, M.

    2006-01-01

    Background. Antitumour schedule-dependency of the doxorubicin and vinblastine combination was explored. Materials and methods. Intraperitoneal Ehrlich ascites tumours (EAT) syngeneic to CBA mice were treated with vinblastine or doxorubicin alone, or in combined treatment schedules. Results. Combinations of doxorubicin and vinblastine administered at 48-h, but not at 24-h interval, regardless of the sequence of drugs, significantly reduced the number of tumour cells in the ascites in comparison with all other treatments. In the combined treatment schedules, the predominant morphological changes as well as DNA distribution pattern were dependent on the first drug applied. Regardless of the sequence of the drugs, median survival times of animals did not significantly differ between the treatment groups. Conclusions. The effect of combination of vinblastine and doxorubicin is schedule-dependent. The time interval, but not the sequence of drugs seems to be crucial for the observed effect. The data from preclinical studies are important for planning combined treatment schedules in clinical setting. (author)

  18. Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.

    Directory of Open Access Journals (Sweden)

    Zhenchuan Song

    Full Text Available Breast cancer is a leading cause of death in women and with an increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based drug is conventional used on breast cancer clinical chemotherapy. However, the drug resistances limited the curative effect of the doxorubicin therapy in breast cancer patients, but the molecular mechanism determinants of breast cancer resistance to doxorubicin chemotherapy are not fully understood. In order to explore the association between metadherin (MTDH and doxorubicin sensitivity, the differential expressions of MTDH in breast cancer cell lines and the sensitivity to doxorubicin of breast cancer cell lines were investigated.The mRNA and protein expression of MTDH were determined by real-time PCR and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S, MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell cycle assay and apoptosis rate was determined by flow cytometry.MCF-7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest expression of MTDH. After MTDH gene was knocked down, the cell proliferation was inhibited, and the inhibitory rate of cell growth and apoptosis rate were enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of doxorubicin treatment. On the other hand, the opposite results were observed in MDA-MB-231 cells with overexpressed MTDH gene.MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.

  19. High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

    International Nuclear Information System (INIS)

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

    2008-01-01

    Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD 10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

  20. Redox-responsive core cross-linked prodrug micelles prepared by click chemistry for pH-triggered doxorubicin delivery

    Directory of Open Access Journals (Sweden)

    X. T. Cao

    2017-10-01

    Full Text Available A pH-triggered drug delivery system of degradable core cross-linked (CCL prodrug micelles was prepared by click chemistry. Doxorubicin conjugated block copolymers of azido functional poly(ethylene oxide-b-poly(glycidyl methacrylate were synthesized by the combination of RAFT polymerization, epoxide ring-opening reaction, and acid-cleavable hydrazone linkages. The CCL prodrug micelles were produced by the reaction of dipropargyl 3,3′-dithiodipropionate and dipropargyl adipate cross-linking agents with the azido groups of the micellar core via alkyne-azide click reaction, which were denoted as CCL/SS and CCL/noSS, respectively. The TEM images of CCL/SS prodrug micelles showed a spherical shape with the average diameter of 61.0 nm from water, and the shape was maintained with an increased diameter upon dilution with 5-fold DMF. The high DOX conjugation efficiency was 88.4%. In contrast to a very slow DOX release from CCL/SS prodrug micelles under the physiological condition (pH 7.4, the drug release is much faster (90% at pH 5.0 and 10 mM of GSH after 96 h. The cytotoxicity test and confocal laser scanning microscopy analysis revealed that CCL/SS prodrug micelles had much enhanced intracellular drug release capability in HepG2 cells than CCL/noSS prodrug micelles.

  1. phenylalanine and l-tyrosine as chiral micellar media for the cat

    African Journals Online (AJOL)

    potential chiral micellar catalysts for the Diels-Alder reaction between methyl acrylate and .... hydrophobic effects, electrostatic interactions and the accompanying medium effects. In the case .... liquids as effective organocatalysts for Diels-Alder reaction. Green Chem. 2014, 16 .... Colloids and Surfaces A: Physicochem.

  2. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status

    Directory of Open Access Journals (Sweden)

    Miraglia Sandra M

    2010-01-01

    Full Text Available Abstract Background Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out. Methods Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg, Amifostine (400 mg/kg, Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin and Sham Control (0.9% saline solution. "Standard One Way Anova" parametric and "Anova on Ranks" non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p Results The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration. Conclusions These results suggest that

  3. Retention of bile salts in micellar electrokinetic chromatography: relation of capacity factor to octanol-water partition coefficient and critical micellar concentration.

    Science.gov (United States)

    Lucangioli, S E; Carducci, C N; Tripodi, V P; Kenndler, E

    2001-12-25

    The capacity factors of 16 anionic cholates (from six bile salts, including their glyco- and tauro-conjugates) were determined in a micellar electrokinetic chromatography (MEKC) system consisting of buffer, pH 7.5 (phosphate-boric acid; 20 mmol/l) with 50 mmol/l sodium dodecyl sulfate (SDS) as micelle former and 10% acetonitrile as organic modifier. The capacity factors of the fully dissociated, negatively charged analytes (ranging between 0.2 and 60) were calculated from their mobilities, with a reference background electrolyte (BGE) without SDS representing "free" solution. For comparison, the capacity factors were derived for a second reference BGE where the SDS concentration (5 mmol/l) is close to the critical micellar concentration (CMC). The capacity factors are compared with the logarithm of the octanol-water partition coefficient, log Pow, as measure for lipophilicity. Clear disagreement between these two parameters is found especially for epimeric cholates with the hydroxy group in position 7. In contrast, fair relation between the capacity factor of the analytes and their CMC is observed both depending strongly on the orientation of the OH groups, and tauro-conjugation as well. In this respect the retention behaviour of the bile salts in MEKC seems to reflect their role as detergents in living systems, and might serve as model parameter beyond lipophilicity.

  4. Correction to: Direct effects of doxorubicin on skeletal muscle contribute to fatigue

    NARCIS (Netherlands)

    Norren, van K.; Helvoort, van A.; Agriles, J.M.; Tuijl, van S.; Arts, K.; Gorselink, M.; Laviano, A.; Kegler, D.; Haagsman, H.P.; Beek, van der E.M.

    2009-01-01

    Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation

  5. New approaches in the management of advanced breast cancer – role of combination treatment with liposomal doxorubicin

    Directory of Open Access Journals (Sweden)

    Iain RJ Macpherson

    2009-08-01

    Full Text Available Iain RJ Macpherson, TR Jeffry EvansBeatson West of Scotland Cancer Centre, Glasgow, United KingdomAbstract: Metastatic breast cancer (MBC remains a major cause of morbidity and mortality in women worldwide. For three decades doxorubicin, alone or in combination with other cytotoxic agents, has been a mainstay of systemic therapy for MBC. However, its use is limited by cumulative cardiotoxicity. More recently liposomal formulations of doxorubicin have been developed which exhibit equal efficacy but reduced cardiotoxicity in comparison to conventional doxorubicin. The novel toxicity profile of liposomal doxorubicins has prompted their evaluation with various cytotoxic agents in patients with MBC. In addition, their favorable cardiac safety profile has prompted re-evaluation of concomitant therapy with doxorubicin and trastuzumab, a regimen of proven efficacy in MBC but previously considered to be associated with significant cardiotoxicity. We review clinical trial data addressing combination therapy with both pegylated and non-pegylated liposomal doxorubicin in patients with MBC.Keywords: breast cancer, anthracycline, liposome-encapsulated doxorubicin, pegylated liposomal doxorubicin, cardiotoxicity

  6. Modulated photophysics of 2-anthracene sulphonate in micellar assembly

    International Nuclear Information System (INIS)

    Rana, Dipak Kumar; Sarkar, Arindam; Dhar, Sayaree; Mandal, Tapas Kumar; Bhattacharya, Subhash Chandra

    2010-01-01

    The association of a non-ionic surfactant of polyoxyethylene-p-(1,1,3,3-tetramethylbutyl)phenyl ether (Triton X) series with 2-AS in aqueous solution has been studied by means of steady-state, time-resolved fluorescence and fluorescence anisotropy techniques. The effect of the hydrophobic chain length on the structural dynamism of the fluorophore has been reported. Experimental results demonstrate that the equilibrium of this dynamism is sensitive to the environment. The association constant of the probe molecule with the non-ionic micelles of Triton X (TX), location of the probe in the micellar environment, have been determined from the change in emission characteristics of the probe as a function of surfactant concentration. The rate constant of quenching and mode of quenching of probe in micellar media have been ascertained. Quantitative estimates of the micropolarity at the binding sites of the probe molecule have been determined. Some of the environment-dependent relevant fluorescence parameters, fluorescence anisotropy (r), have been monitored for exploring the imposed motional restriction of the microenvironment around the probe. An attempt has been made to correlate the steady-state results with time resolved study.

  7. Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

    Science.gov (United States)

    Lee, Kwang-Hun; Liapi, Eleni A; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A; Ventura, Veronica Prieto; Geschwind, Jean-Francois H

    2010-06-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  8. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    International Nuclear Information System (INIS)

    Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

    2010-01-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  9. Evolution of ZnS Nanoparticles via Facile CTAB Aqueous Micellar Solution Route: A Study on Controlling Parameters

    Directory of Open Access Journals (Sweden)

    Gradzielski Michael

    2008-01-01

    Full Text Available Abstract Synthesis of semiconductor nanoparticles with new photophysical properties is an area of special interest. Here, we report synthesis of ZnS nanoparticles in aqueous micellar solution of Cetyltrimethylammonium bromide (CTAB. The size of ZnS nanodispersions in aqueous micellar solution has been calculated using UV-vis spectroscopy, XRD, SAXS, and TEM measurements. The nanoparticles are found to be polydispersed in the size range 6–15 nm. Surface passivation by surfactant molecules has been studied using FTIR and fluorescence spectroscopy. The nanoparticles have been better stabilized using CTAB concentration above 1 mM. Furthermore, room temperature absorption and fluorescence emission of powdered ZnS nanoparticles after redispersion in water have also been investigated and compared with that in aqueous micellar solution. Time-dependent absorption behavior reveals that the formation of ZnS nanoparticles depends on CTAB concentration and was complete within 25 min.

  10. Effect of tartarate and citrate based food additives on the micellar properties of sodium dodecylsulfate for prospective use as food emulsifier.

    Science.gov (United States)

    Banipal, Tarlok S; Kaur, Harjinder; Kaur, Amanpreet; Banipal, Parampaul K

    2016-01-01

    Citrate and tartarate based food preservatives can be used to enhance the emulsifying properties of sodium dodecylsulfate (SDS) based micellar system and thus making it appropriate for food applications. Exploration of interactions between the two species is the key constraint for execution of such ideas. In this work various micellar and thermodynamic parameters of SDS like critical micellar concentration (CMC), standard Gibbs free energy of micellization (ΔG(0)mic.) etc. have been calculated in different concentrations of disodium tartarate (DST) and trisodium citrate (TSC) in the temperature range (288.15-318.15)K from the conductivity and surface tension measurements. The parameters obtained from these studies reveal the competitive nature of both the additives with SDS for available positions at the air/water interface. TSC is found to be more effective additive in order to make SDS micellar system better for its potential applications as food emulsifier. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Determination of patulin in commercial apple juice by micellar electrokinetic chromatography.

    Science.gov (United States)

    Murillo, M; González-Peñas, E; Amézqueta, S

    2008-01-01

    A novel and validated micellar electrokinetic capillary chromatography (MEKC) method using ultraviolet detection (UV) has been applied to the quantitative analysis of patulin (PAT) in commercial apple juice. Patulin was extracted from samples with an ethylacetate solution. The micellar electrokinetic capillary chromatography (MECK) parameters studied for method optimization were buffer composition, voltage, temperature, and a separation between PAT and 5-hydroxymethylfurfural (HMF) (main interference in apple juice PAT analysis) peaks until reaching baseline. The method passes a series of validation tests including selectivity, linearity, limit of detection and quantification (0.7 and 2.5 microgL(-1), respectively), precision (within and between-day variability) and recovery (80.2% RSD=4%), accuracy, and robustness. This method was successfully applied to the measurement of 20 apple juice samples obtained from different supermarkets. One hundred percent of the samples were contaminated with a level greater than the limit of detection, with mean and median values of 41.3 and 35.7 microgL(-1), respectively.

  12. Thermodynamic analysis of unimer-micelle and sphere-to-rod micellar transitions of aqueous solutions of sodium dodecylbenzenesulfonate

    International Nuclear Information System (INIS)

    Valente, Artur J.M.; López Cascales, J.J.; Fernández Romero, Antonio J.

    2014-01-01

    Highlights: • Unimer-micelle and sphere-to-rod micellar transitions were observed to sodium dodecylbenzenesulfonate in aqueous solutions. • Two micellar transitions were seen by electrical conductivity and surface tension. • An anomalous ΔS 0 and ΔH 0 increase with T was found for the second critical transition. • More stable aggregates are evidenced for spherical micelles than for the other shapes. - Abstract: Temperature dependence of specific conductivity of sodium dodecylbenzenesulfonate (NaDBS) aqueous solutions was analyzed. Two breaks on the plot appeared for all temperature, which suggest two micellar transitions. This has been corroborated by surface tension measurements. The first transition concentration occurs at the critical micelle concentration (CMC), whilst the second critical concentration (so-called transition micellar concentration, TMC) is due to a sphere-to-rod micelles transition. The dependence of CMC and TMC on the temperature allows the computation of the corresponding thermodynamic functions: Gibbs free energy, enthalpy and entropy changes. For the CMC, enthalpy and entropy increments were found that decrease with the temperature values. However, an anomalous behavior was obtained for the TMC, where both ΔS 0 and ΔH 0 values raised with the temperature increase. However, for both transitions, an (enthalpy + entropy) compensation is observed. These results will be compared with similar systems reported in the literature

  13. Probing the amphiphile micellar to hexagonal phase transition using Positron Annihilation Lifetime Spectroscopy.

    Science.gov (United States)

    Dong, Aurelia W; Fong, Celesta; Hill, Anita J; Boyd, Ben J; Drummond, Calum J

    2013-07-15

    Positron Annihilation Lifetime Spectroscopy (PALS) has been utilised only sparingly for structural characterisation in self assembled materials. Inconsistencies in approaches to experimental configuration and data analysis between studies has complicated comparisons between studies, meaning that the technique has not provided a cohesive data set across the study of different self assembled systems that advance the technique towards an important tool in soft matter research. In the current work a systematic study was conducted using ionic and non-ionic micellar systems with increasing surfactant concentration to probe positron behaviour on changes between micellar phase structures, and data analysed using contemporary approaches to fit four component spectra. A characteristic orthopositronium lifetime (in the organic regions) of 3.5±0.2 ns was obtained for the hexagonal phase for surfactants with C12 alkyl chains. Chemical quenching of the positron species was also observed for systems with ionic amphiphiles. The application of PALS has also highlighted an inconsistency in the published phase diagram for the octa(ethylene oxide) monododecyl ether (C12EO8) system. These results provide new insight into how the physical properties of micellar systems can be related to PALS parameters and means that the PALS technique can be applied to other more complex self-assembled amphiphile systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells.

    Science.gov (United States)

    Dangkong, Darinee; Limpanasithikul, Wacharee

    2015-02-01

    Doxorubicin is a chemotherapy agent used in non-Hodgkin's lymphoma but side effects limit its use. Citral is a mixture of neral and geranial found in essential oils of lemon grass. We evaluated the activity of citral, doxorubicin, and combination on cytotoxicity, apoptosis, and anti-proliferative effects using human lymphoma Ramos cells. Cells were treated with doxorubicin alone or in combination with citral (10, 20, and 40 μM). Cytotoxic and apoptosis studies were done after 24 and 18 h incubations, respectively. Cytotoxic effects of citral on normal human peripheral blood mononuclear cells (PBMCs) were also investigated for its safety. Changes in the expression of BCL-2 family genes were analyzed by quantitative RT-PCR. Citral had cytotoxicity on cells with an IC50 value of 77.19 ± 4.95 µM. Citral at concentrations of 10, 20, and 40 µM additively increased the cytotoxic and apoptotic effects of doxorubicin, leading to decreased IC50 (µM) of the drug from 2.50 ± 0.01 to 2.16 ± 0.03, 1.90 ± 0.04, and 1.23 ± 0.04, respectively. Enhanced cytotoxicity was not observed in normal human PBMCs. Citral (40 µM) in combination with doxorubicin (1.5 µM) increased the expression of pro-apoptotic protein BAK but significantly decreased the expression of anti-apoptotic protein BCL-XL to 5.26-fold compared with doxorubicin-treated cells. It did not change the anti-proliferative activity of drug. Citral potentiated cytotoxicity of doxorubicin by increasing apoptotic effects. We conclude that citral may have beneficial effects in patients with B cell lymphoma treated with chemotherapy.

  15. The influence of P-glycoprotein expression and its inhibitors on the distribution of doxorubicin in breast tumors

    International Nuclear Information System (INIS)

    Patel, Krupa J; Tannock, Ian F

    2009-01-01

    Anti-cancer drugs access solid tumors via blood vessels, and must penetrate tumor tissue to reach all cancer cells. Previous studies have demonstrated steep gradients of decreasing doxorubicin fluorescence with increasing distance from blood vessels, such that many tumor cells are not exposed to drug. Studies using multilayered cell cultures show that increased P-glycoprotein (PgP) is associated with better penetration of doxorubicin, while PgP inhibitors decrease drug penetration in tumor tissue. Here we evaluate the effect of PgP expression on doxorubicin distribution in vivo. Mice bearing tumor sublines with either high or low expression of PgP were treated with doxorubicin, with or without pre-treatment with the PgP inhibitors verapamil or PSC 833. The distribution of doxorubicin in relation to tumor blood vessels was quantified using immunofluorescence. Our results indicate greater uptake of doxorubicin by cells near blood vessels in wild type as compared to PgP-overexpressing tumors, and pre-treatment with verapamil or PSC 833 increased uptake in PgP-overexpressing tumors. However, there were steeper gradients of decreasing doxorubicin fluorescence in wild-type tumors compared to PgP overexpressing tumors, and treatment of PgP overexpressing tumors with PgP inhibitors led to steeper gradients and greater heterogeneity in the distribution of doxorubicin. PgP inhibitors increase uptake of doxorubicin in cells close to blood vessels, have little effect on drug uptake into cells at intermediate distances, and might have a paradoxical effect to decrease doxorubicin uptake into distal cells. This effect probably contributes to the limited success of PgP inhibitors in clinical trials

  16. phenylalanine and l-tyrosine as chiral micellar media for the cat

    African Journals Online (AJOL)

    polar solvents [15-18]. Hence, surfactants offer the possibility for organic reactions to occur in aqueous media, and from the viewpoint of green chemistry, water is safer, harmless and environmentally benign [19]. However, there has been limited work on the use of chiral micellar media to catalyze Diels-. Alder reactions.

  17. S-diclofenac Protects against Doxorubicin-Induced Cardiomyopathy in Mice via Ameliorating Cardiac Gap Junction Remodeling

    Science.gov (United States)

    Zhang, Huili; Zhang, Alian; Guo, Changfa; Shi, Chunzhi; Zhang, Yang; Liu, Qing; Sparatore, Anna; Wang, Changqian

    2011-01-01

    Hydrogen sulfide (H2S), as a novel gaseous mediator, plays important roles in mammalian cardiovascular tissues. In the present study, we investigated the cardioprotective effect of S-diclofenac (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester), a novel H2S-releasing derivative of diclofenac, in a murine model of doxorubicin-induced cardiomyopathy. After a single dose injection of doxorubicin (15 mg/kg, i.p.), male C57BL/6J mice were given daily treatment of S-diclofenac (25 and 50 µmol/kg, i.p.), diclofenac (25 and 50 µmol/kg, i.p.), NaHS (50 µmol/kg, i.p.), or same volume of vehicle. The cardioprotective effect of S-diclofenac was observed after 14 days. It showed that S-diclofenac, but not diclofenac, dose-dependently inhibited the doxorubicin-induced downregulation of cardiac gap junction proteins (connexin 43 and connexin 45) and thus reversed the remodeling of gap junctions in hearts. It also dose-dependently suppressed doxorubicin-induced activation of JNK in hearts. Furthermore, S-diclofenac produced a dose-dependent anti-inflammatory and anti-oxidative effect in this model. As a result, S-diclofenac significantly attenuated doxorubicin-related cardiac injury and cardiac dysfunction, and improved the survival rate of mice with doxorubicin-induced cardiomyopathy. These effects of S-diclofenac were mimicked in large part by NaHS. Therefore, we propose that H2S released from S-diclofenac in vivo contributes to the protective effect in doxorubicin-induced cardiomyopathy. These data also provide evidence for a critical role of H2S in the pathogenesis of doxorubicin-induced cardiomyopathy. PMID:22039489

  18. Interactions between N-acetyl-L-cysteine protected CdTe quantum dots and doxorubicin through spectroscopic method

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiupei, E-mail: xiupeiyang@163.com [Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province, Nanchong 637000 (China); College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000 (China); Lin, Jia; Liao, Xiulin; Zong, Yingying; Gao, Huanhuan [College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000 (China)

    2015-06-15

    Highlights: • CdTe quantum dots with the diameter of 3–5 nm were synthesized in aqueous solution. • The modified CdTe quantum dots showed well fluorescence properties. • The interaction between the CdTe quantum dots and doxorubicin (DR) was investigated. - Abstract: N-acetyl-L-cysteine protected cadmium telluride quantum dots with a diameter of 3–5 nm were synthesized in aqueous solution. The interaction between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin was investigated by ultraviolet–visible absorption and fluorescence spectroscopy at physiological conditions (pH 7.2, 37 °C). The results indicate that electron transfer has occurred between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin under light illumination. The quantum dots react readily with doxorubicin to form a N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex via electrostatic attraction between the −NH{sub 3}{sup +} moiety of doxorubicin and the −COO{sup −} moiety of N-acetyl-L-cysteine/cadmium telluride quantum dots. The interaction of N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex with bovine serum albumin was studied as well, showing that the complex might induce the conformation change of bovine serum due to changes in microenvironment of bovine serum.

  19. Interactions between N-acetyl-L-cysteine protected CdTe quantum dots and doxorubicin through spectroscopic method

    International Nuclear Information System (INIS)

    Yang, Xiupei; Lin, Jia; Liao, Xiulin; Zong, Yingying; Gao, Huanhuan

    2015-01-01

    Highlights: • CdTe quantum dots with the diameter of 3–5 nm were synthesized in aqueous solution. • The modified CdTe quantum dots showed well fluorescence properties. • The interaction between the CdTe quantum dots and doxorubicin (DR) was investigated. - Abstract: N-acetyl-L-cysteine protected cadmium telluride quantum dots with a diameter of 3–5 nm were synthesized in aqueous solution. The interaction between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin was investigated by ultraviolet–visible absorption and fluorescence spectroscopy at physiological conditions (pH 7.2, 37 °C). The results indicate that electron transfer has occurred between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin under light illumination. The quantum dots react readily with doxorubicin to form a N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex via electrostatic attraction between the −NH 3 + moiety of doxorubicin and the −COO − moiety of N-acetyl-L-cysteine/cadmium telluride quantum dots. The interaction of N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex with bovine serum albumin was studied as well, showing that the complex might induce the conformation change of bovine serum due to changes in microenvironment of bovine serum

  20. Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2017-12-01

    Full Text Available This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the prostate cancer cells. The prostate cancer targeting was mediated by the AntiSar antibodies decorated surface of the nanocage. Formation of the chitosan nanoparticles was determined using a ninhydrin assay and differential pulse voltammetry. Obtained results showed the strong effect of tripolyphosphine on the nanoparticle formation. The zinc ions affected strong chitosan backbone coiling both in inner and outer chitosan nanoparticle structure. Zinc electrochemical signal depended on the level of the complex formation and the potential shift from −960 to −950 mV. Formed complex is suitable for doxorubicin delivery. It was observed the 20% entrapment efficiency of doxorubicin and strong dependence of drug release after 120 min in the blood environment. The functionality of the designed nanotransporter was proven. The purposed determination showed linear dependence in the concentration range of Anti-sarcosine IgG labeled gold nanoparticles from 0 to 1000 µg/mL and the regression equation was found to be y = 3.8x − 66.7 and R2 = 0.99. Performed ELISA confirmed the ability of Anti-sarcosine IgG labeled chitosan nanoparticles with loaded doxorubicin to bind to the sarcosine molecule. Observed hemolytic activity of the nanotransporter was 40%. Inhibition activity of our proposed nanotransporter was evaluated to be 0% on the experimental model of S. cerevisiae. Anti-sarcosine IgG labeled chitosan nanoparticles, with loaded doxorubicin stabilized by Zn ions, are a perspective type of nanocarrier for targeted drug therapy managed by specific interaction with sarcosine and metallothionein for prostate cancer.

  1. Phase behavior and micellar properties of carboxylic acid end group modified pluronic surfactants

    NARCIS (Netherlands)

    Custers, J.P.A.; Broeke, van den L.J.P.; Keurentjes, J.T.F.

    2007-01-01

    The micellar behavior of three different carboxylic acid end standing (CAE) surfactants has been characterized using conductometry, differential scanning calorimetry, isothermal titration calorimetry, and dynamic light scattering. The CAE surfactants are modified high molecular weight Pluronic

  2. Structural study of the AOT reverse micellar system. Influence of attractive interactions induced by the solubilisation of native and modified proteins

    International Nuclear Information System (INIS)

    Cassin, Guillaume

    1994-01-01

    This research thesis reports the study of the influence of intra-micellar attractions on the thermodynamic behaviour of reverse micellar systems, as well as of the effects induced by the solubilisation of natives or modified proteins. The author proposes a model to explain the decrease of attractions between droplets when the volume fraction occupied by reverse micelles increases. This model which highlights the importance of depletion forces between reverse micelles, allows the building up of a theoretical relationship between the bonding parameter and the volume fraction of reverse micelles. In order to understand the appearance of an attractive term related to the solubilisation of native cytochrome-c in these systems, this protein has been chemically modified. The author highlights the role of the charge born by a micellar probe on the thermodynamic behaviour of micro-emulsions. Then, the author applies the model of dimerizing adhesive spheres to reverse micellar systems containing native cytochrome-c. He shows that theoretical predictions of this model are in agreement with obtained experimental results [fr

  3. Computer Color Matching and Levelness of PEG-Based Reverse Micellar Decamethyl cyclopentasiloxane (D5 Solvent-Assisted Reactive Dyeing on Cotton Fiber

    Directory of Open Access Journals (Sweden)

    Alan Y. L. Tang

    2017-07-01

    Full Text Available The color matching and levelness of cotton fabrics dyed with reactive dye, in a non-aqueous environmentally-friendly medium of decamethylcyclopentasiloxane (D5, was investigated using the non-ionic surfactant reverse-micellar approach comprised of poly(ethylene glycol-based surfactant. The calibration dyeing databases for both conventional water-based dyeing and D5-assisted reverse micellar dyeing were established, along with the dyeing of standard samples with predetermined concentrations. Computer color matching (CCM was conducted by using different color difference formulae for both dyeing methods. Experimental results reveal that the measured concentrations were nearly the same as the expected concentrations for both methods. This indicates that the D5-assisted non-ionic reverse micellar dyeing approach can achieve color matching as good as the conventional dyeing system. The levelness of the dyed samples was measured according to the relative unlevelness indices (RUI, and the results reveal that the samples dyed by the D5 reverse micellar dyeing system can achieve good to excellent levelness comparable to that of the conventional dyeing system.

  4. Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.

    Science.gov (United States)

    Batist, G; Ramakrishnan, G; Rao, C S; Chandrasekharan, A; Gutheil, J; Guthrie, T; Shah, P; Khojasteh, A; Nair, M K; Hoelzer, K; Tkaczuk, K; Park, Y C; Lee, L W

    2001-03-01

    To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.

  5. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Science.gov (United States)

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 μM, 24 h) prevented doxorubicin (0.5 μM, 24 h)-induced elevation of diastolic [Ca2+]i, the slowing of [Ca2+]i relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermore, pretreatment with TVP1022 attenuated the doxorubicin-induced reduction in the protein expression of sarco/endoplasmic reticulum calcium (Ca2+) ATPase, Na+/Ca2+ exchanger 1, and total connexin 43. Finally, TVP1022 diminished the inhibitory effect of doxorubicin on gap junctional intercellular coupling (measured by means of Lucifer yellow transfer) and on conduction velocity, the amplitude of the activation phase, and the maximal rate of activation (dv/dtmax) measured by the Micro-Electrode-Array system. In summary, our results indicate that TVP1022 acts as a novel cardioprotective agent against anthracycline cardiotoxicity, and therefore potentially can be coadmhence, the inistered with doxorubicin in the treatment of malignancies in humans. PMID:19915070

  6. SIRT1 Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the Oxidative Stress and p38MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Yang Ruan

    2015-02-01

    Full Text Available Background: SIRT1, which belongs to the Sirtuin family of NAD-dependent enzymes, plays diverse roles in aging, metabolism, and disease biology. It could regulate cell survival and has been shown to be a protective factor in heart function. Hence, we verified the mechanism by which SIRT1 regulates doxorubicin induced cardiomyocyte injury in vivo and in vitro. Methods: We analyzed SIRT1 expression in doxorubicin-induced neonatal rat cardiomyocyte injury model and adult mouse heart failure model. SIRT1 was over-expressed in cultured neonatal rat cardiomyocyte by adenovirus mediated gene transfer. SIRT1 agonist resveratrol was used to treat the doxorubicin-induced heart failure mouse model. Echocardiography, reactive oxygen species (ROS production, TUNEL, qRT-PCR, and Western blotting were performed to analyze cell survival, oxidative stress, and inflammatory signal pathways in cardiomyocytes. Results: SIRT1 expression was down-regulated in doxorubicin induced cardiomocyte injury, accompanied by elevated oxidative stress and cell apoptosis. SIRT1 over-expression reduced doxorubicin induced cardiomyocyte apoptosis with the attenuated ROS production. SIRT1 also reduced cell apoptosis by inhibition of p38MAPK phosphorylation and caspase-3 activation. The SIRT1 agonist resveratrol was able to prevent doxorubicin-induced heart function loss. Moreover, the SIRT1 inhibitor niacinamide could reverse SIRT1's protective effect in cultured neonatal rat cardiomyocytes. Conclusions: These results support the role of SIRT1 as an important regulator of cardiomyocyte apoptosis during doxorubicin-induced heart injury, which may represent a potential therapeutic target for doxorubicin-induced cardiomyopathy.

  7. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

    Science.gov (United States)

    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

    2016-03-31

    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  8. Intermolecular electron transfer between coumarin dyes and aromatic amines in Triton-X-100 micellar solutions: Evidence for Marcus inverted region

    Science.gov (United States)

    Kumbhakar, Manoj; Nath, Sukhendu; Mukherjee, Tulsi; Pal, Haridas

    2004-02-01

    Photoinduced electron transfer (ET) between coumarin dyes and aromatic amines has been investigated in Triton-X-100 micellar solutions and the results have been compared with those observed earlier in homogeneous medium. Significant static quenching of the coumarin fluorescence due to the presence of high concentration of amines around the coumarin fluorophore in the micelles has been observed in steady-state fluorescence studies. Time-resolved studies with nanosecond resolutions mostly show the dynamic part of the quenching for the excited coumarin dyes by the amine quenchers. A correlation of the quenching rate constants, estimated from the time-resolved measurements, with the free energy changes (ΔG0) of the ET reactions shows the typical bell shaped curve as predicted by Marcus outer-sphere ET theory. The inversion in the ET rates for the present systems occurs at an exergonicity (-ΔG0) of ~0.7-0.8 eV, which is unusually low considering the polarity of the Palisade layer of the micelles where the reactants reside. Present results have been rationalized on the basis of the two dimensional ET model assuming that the solvent relaxation in micellar media is much slower than the rate of the ET process. Detailed analysis of the experimental data shows that the diffusional model of the bimolecular quenching kinetics is not applicable for the ET reactions in the micellar solutions. In the present systems, the reactions can be better visualized as equivalent to intramolecular electron transfer processes, with statistical distribution of the donors and acceptors in the micelles. A low electron coupling (Vel) parameter is estimated from the correlation of the experimentally observed and the theoretically calculated ET rates, which indicates that the average donor-acceptor separation in the micellar ET reactions is substantially larger than for the donor-acceptor contact distance. Comparison of the Vel values in the micellar solution and in the donor-acceptor close

  9. Doxorubicin-Induced Gut Toxicity in Piglets fed Bovine Milk and Colostrum

    DEFF Research Database (Denmark)

    Shen, René Liang; Rathe, Mathias; Jiang, Pingping

    2016-01-01

    OBJECTIVE: Chemotherapy-induced intestinal toxicity is a common adverse effect of cancer treatment. We hypothesized that a milk diet containing bovine colostrum (BC) would reduce intestinal toxicity in doxorubicin-treated piglets. METHODS: Study 1 investigated intestinal parameters nine days after...... Colostrum supplementation had limited effects on doxorubicin-induced toxicity in milk-fed piglets suggesting that colostrum and a bovine milk diet enriched with whey protein provided similar...

  10. Microstructural evolution of a model, shear-banding micellar solution during shear startup and cessation.

    Science.gov (United States)

    López-Barrón, Carlos R; Gurnon, A Kate; Eberle, Aaron P R; Porcar, Lionel; Wagner, Norman J

    2014-04-01

    We present direct measurements of the evolution of the segmental-level microstructure of a stable shear-banding polymerlike micelle solution during flow startup and cessation in the plane of flow. These measurements provide a definitive, quantitative microstructural understanding of the stages observed during flow startup: an initial elastic response with limited alignment that yields with a large stress overshoot to a homogeneous flow with associated micellar alignment that persists for approximately three relaxation times. This transient is followed by a shear (kink) band formation with a flow-aligned low-viscosity band that exhibits shear-induced concentration fluctuations and coexists with a nearly isotropic band of homogenous, highly viscoelastic micellar solution. Stable, steady banding flow is achieved only after approximately two reptation times. Flow cessation from this shear-banded state is also found to be nontrivial, exhibiting an initial fast relaxation with only minor structural relaxation, followed by a slower relaxation of the aligned micellar fluid with the equilibrium fluid's characteristic relaxation time. These measurements resolve a controversy in the literature surrounding the mechanism of shear banding in entangled wormlike micelles and, by means of comparison to existing literature, provide further insights into the mechanisms driving shear-banding instabilities in related systems. The methods and instrumentation described should find broad use in exploring complex fluid rheology and testing microstructure-based constitutive equations.

  11. Early detection of doxorubicin-induced cariotoxocity and its prevention by alpha-tocopherol

    International Nuclear Information System (INIS)

    Ajmal, K.; Khan, B.T.

    2014-01-01

    To detect doxorubicin-induced myocardial injury by quantitative estimation of cardiospecific protein, Cardiac Troponin I (cTnI) at early stage and to evaluate the cardioprotective effects of Tocopherol. Study Design: Labbased randomized controlled in-vivo study in rabbits. Place and Duration of Study: Department of Pharmacology in collaboration with Pathology department, Army Medical College Rawalpindi, Pakistan from Jan 2012 to Dec 2012. Material and Methods: Eighteen healthy male adult rabbits were used. Cardiotoxicity was induced by single intravenous injection of 12 mg /kg of doxorubicin in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pretreated with Tocopherol 200 mg/kg of body weight for ten days before injection of doxorubicin 12mg/kg. Results: Doxorubicin produced severe cardiotoxicity confirmed by markedly raised serum levels of cTnI, CK-MB, LDH and grade 3 necrosis of the heart issue in rabbits. The pre-treatment with Tocopherol resulted in improved serum levels of cTnI and the histological picture of heart tissue. Conclusions: The quantitative cTnI estimation for detection of cardiotoxicity at subclinical level can lead to significant economic impact in management of cancer patients because the troponin-negative subjects can be excluded from long term cardiac monitoring programs, which require high cost imaging techniques. Furthermore, the outcome of most potent and widely used doxorubicin chemotherapy can be made successful with the concurrent use of alpha-Tocopherol. (author)

  12. Micellar and antibody-targeted polymer therapeutics

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Chytil, Petr; Kovář, Lubomír; Říhová, Blanka; Ulbrich, Karel

    2010-01-01

    Roč. 295, - (2010), s. 1-12 ISSN 1022-1360. [Prague Meetings on Macromolecules /73./ New Frontiers in Macromolecular Science: From Macromolecular Concepts of Living Matter to Polymers for Better Quality of Life. Prague, 05.07.2009-09.07.2009] R&D Projects: GA AV ČR IAA400500806; GA AV ČR IAAX00500803; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : doxorubicin * drug delivery systems * HPMA copolymers Subject RIV: CD - Macromolecular Chemistry

  13. Cellular robustness conferred by genetic crosstalk underlies resistance against chemotherapeutic drug doxorubicin in fission yeast.

    Directory of Open Access Journals (Sweden)

    Zoey Tay

    Full Text Available Doxorubicin is an anthracycline antibiotic that is among one of the most commonly used chemotherapeutic agents in the clinical setting. The usage of doxorubicin is faced with many problems including severe side effects and chemoresistance. To overcome these challenges, it is important to gain an understanding of the underlying molecular mechanisms with regards to the mode of action of doxorubicin. To facilitate this aim, we identified the genes that are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe. We further demonstrated interplay between factors controlling various aspects of chromosome metabolism, mitochondrial respiration and membrane transport. In the nucleus we observed that the subunits of the Ino80, RSC, and SAGA complexes function in the similar epistatic group that shares significant overlap with the homologous recombination genes. However, these factors generally act in synergistic manner with the chromosome segregation regulator DASH complex proteins, possibly forming two major arms for regulating doxorubicin resistance in the nucleus. Simultaneous disruption of genes function in membrane efflux transport or the mitochondrial respiratory chain integrity in the mutants defective in either Ino80 or HR function resulted in cumulative upregulation of drug-specific growth defects, suggesting a rewiring of pathways that synergize only when the cells is exposed to the cytotoxic stress. Taken together, our work not only identified factors that are required for survival of the cells in the presence of doxorubicin but has further demonstrated that an extensive molecular crosstalk exists between these factors to robustly confer doxorubicin resistance.

  14. Oxygen radical detoxification enzymes in doxorubicin-sensitive and -resistant P388 murine leukemia cells

    International Nuclear Information System (INIS)

    Ramu, A.; Cohen, L.; Glaubiger, D.

    1984-01-01

    One of the proposed mechanisms for the cytotoxic effects of anthracycline compounds suggests that the effect is mediated through the formation of intracellular superoxide radicals. It is therefore possible that doxorubicin resistance is associated with increased intracellular enzyme capacity to convert these superoxide radicals to inactive metabolites. We have measured the relative activities of superoxide dismutase, glutathione peroxidase, and catalase in P388 mouse leukemia cells and in a doxorubicin-resistant subline. Since oxygen-reactive metabolites also play a role in mediating the cytotoxicity of ionizing radiation, the radiosensitivity of both cell lines was also studied. No significant differences in superoxide dismutase activity between these cell lines was observed, indicating that they have a similar capacity to convert superoxide anion radicals to hydrogen peroxide. P388 cells that are resistant to doxorubicin have 1.5 times the glutathione content and 1.5 times the activity of glutathione peroxidase measured in drug-sensitive P388 cells. However, incubation with 1-chloro-2,4-dinitrobenzene, which covalently binds glutathione, had no effect on the sensitivity of either cell line to doxorubicin. Measured catalase activity in drug-resistant P388 cells was one-third of the activity measured in doxorubicin-sensitive P388 cells. The activity of this enzyme was much higher than that of glutathione peroxidase in terms of H 2 O 2 deactivation in both cell lines. It is therefore unlikely that doxorubicin-resistant P388 cells have an increased ability to detoxify reactive oxygen metabolites when compared to drug-sensitive cells. Doxorubicin-resistant P388 cells were significantly more sensitive to X-irradiation than were drug-sensitive P388 cells. These observations suggest that the difference in catalase activity in these cell lines may be associated with the observed differences in radiosensitivity

  15. Complexation of lysozyme with sodium caseinate and micellar casein in aqueous buffered solutions

    NARCIS (Netherlands)

    Antonov, Y.A.; Moldenaers, P.; Cardinaels, R.M.

    We present an extended structural and morphological study of the complexation of lysozyme (Lys) with sodium caseinate (SC) and micellar casein (MC) by means of turbidity measurements, phase analysis, dynamic, static and electrophoretic light scattering, bright-field and confocal laser scanning

  16. Spectroscopic studies on the molecular interaction between salicylic acid and riboflavin (B{sub 2}) in micellar solution

    Energy Technology Data Exchange (ETDEWEB)

    Bhattar, S.L.; Kolekar, G.B. [Fluorescence Spectroscopy Research Laboratory, Department of Chemistry, Shivaji University, Kolhapur-416 004, Maharashtra (India); Patil, S.R., E-mail: srp_fsl@rediffmail.co [Fluorescence Spectroscopy Research Laboratory, Department of Chemistry, Shivaji University, Kolhapur-416 004, Maharashtra (India)

    2010-03-15

    The interaction between salicylic acid (SA) and riboflavin (RF) was studied by Fluorescence Resonance Energy Transfer (FRET) in micellar solution. The riboflavin strongly quenches the intrinsic fluorescence of SA by radiative energy transfer. The extent of energy transfer in sodium dodecyl sulphate (SDS) micellar solution of different concentration is quantified from the energy transfer efficiency data. It is seen that the energy transfer is more efficient in the micellar solution. The critical energy transfer distance (R{sub 0}) was determined from which the mean distance between SA and RF molecules was calculated. The quenching was found to fit into Stern-Volmer relation. The results on variation of Stern-Volmer constant (K{sub sv}) with quencher concentration obtained at different temperatures suggested the formation of complex between SA and RF. The association constant of complex formation was estimated and found to decrease with temperature. The values of thermodynamic parameters DELTAH, DELTAG and DELTAS at different temperatures were estimated and the results indicated that the molecular interaction between SA and RF is electrostatic in nature.

  17. Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

    Science.gov (United States)

    Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

    2013-08-01

    Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

  18. Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

    Science.gov (United States)

    Yu, Man; Lee, Carol; Wang, Marina; Tannock, Ian F

    2015-10-01

    Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  19. Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin

    Directory of Open Access Journals (Sweden)

    Jiang SP

    2013-08-01

    Full Text Available Sai-Ping Jiang,1,2,* Sai-Nan He,3,* Yun-Long Li,2,3 Da-Lin Feng,2 Xiao-Yang Lu,1 Yong-Zhong Du,2 He-Yong Yu,3 Fu-Qiang Hu,2 Hong Yuan2 1Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 3Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China *These authors contributed equally to this work Purpose: Safe and effective lipid nanoemulsion (LNE formulations for the antitumor delivery of doxorubicin is designed. Methods: LNEs composed of medium-chain triglyceride, soybean oil, lecithin, and doxorubicin are prepared by a solvent-diffusion method in an aqueous system. The effects of lipid material composition and polyethylene glycol (PEGylation on the size, drug encapsulation efficiency, and stability of LNEs are investigated. Based on in-vitro cytotoxicity and cellular uptake tests of A549 (human lung carcinoma cells, in-vivo biodistribution, antitumor activity, and cardiac toxicity are further examined using nude mouse bearing A549 tumor. Results: The LNE size decreases from 126.4 ± 8.7 nm to 44.5 ± 9.3 nm with increased weight ratio of medium-chain triglyceride to soybean oil from 1:4 to 3:2, whereas the encapsulation efficiency of doxorubicin is slightly reduced from 79.2% ± 2.1% to 71.2% ± 2.9%. The PEGylation of LNE by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(PEG2000] (DSPE-PEG 2000 does not significantly change the size and drug encapsulation efficiency. Three-month storage at room temperature and lyophilization process does not affect the drug encapsulation efficiency, whereas the size slightly increases to almost 100 nm. The in-vitro drug-release profiles of LNEs suggest that the present formulation can prolong drug release for 48 hours. LNEs can be internalized into tumor cells in vitro and efficiently accumulate in tumor tissues in vivo by passive targeting

  20. A sensitive high performance liquid chromatography assay for the quantification of doxorubicin associated with DNA in tumor and tissues.

    Science.gov (United States)

    Lucas, Andrew T; O'Neal, Sara K; Santos, Charlene M; White, Taylor F; Zamboni, William C

    2016-02-05

    Doxorubicin, a widely used anticancer agent, exhibits antitumor activity against a wide variety of malignancies. The drug exerts its cytotoxic effects by binding to and intercalating within the DNA of tumor and tissue cells. However, current assays are unable to accurately determine the concentration of the intracellular active form of doxorubicin. Thus, the development of a sample processing method and a high-performance liquid chromatography (HPLC) methodology was performed in order to quantify doxorubicin that is associated with DNA in tumors and tissues, which provided an intracellular cytotoxic measure of doxorubicin exposure after administration of small molecule and nanoparticle formulations of doxorubicin. The assay uses daunorubicin as an internal standard; liquid-liquid phase extraction to isolate drug associated with DNA; a Shimadzu HPLC with fluorescence detection equipped with a Phenomenex Luna C18 (2μm, 2.0×100mm) analytical column and a gradient mobile phase of 0.1% formic acid in water or acetonitrile for separation and quantification. The assay has a lower limit of detection (LLOQ) of 10ng/mL and is shown to be linear up to 3000ng/mL. The intra- and inter-day precision of the assay expressed as a coefficient of variation (CV%) ranged from 4.01 to 8.81%. Furthermore, the suitability of this assay for measuring doxorubicin associated with DNA in vivo was demonstrated by using it to quantify the doxorubicin concentration within tumor samples from SKOV3 and HEC1A mice obtained 72h after administration of PEGylated liposomal doxorubicin (Doxil(®); PLD) at 6mg/kg IV x 1. This HPLC assay allows for sensitive intracellular quantification of doxorubicin and will be an important tool for future studies evaluating intracellular pharmacokinetics of doxorubicin and various nanoparticle formulations of doxorubicin. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Essential Oil from Myrica rubra Leaves Potentiated Antiproliferative and Prooxidative Effect of Doxorubicin and its Accumulation in Intestinal Cancer Cells.

    Science.gov (United States)

    Ambrož, Martin; Hanušová, Veronika; Skarka, Adam; Boušová, Iva; Králová, Věra; Langhasová, Lenka; Skálová, Lenka

    2016-01-01

    Essential oil from the leaves of Myrica rubra, a subtropical Asian fruit tree traditionally used in folk medicines, has a significant antiproliferative effect in several intestinal cancer cell lines. Doxorubicin belongs to the most important cytostatics used in cancer therapy. The present study was designed to evaluate the effects of defined essential oil from M. rubra leaves on efficacy, prooxidative effect, and accumulation of doxorubicin in cancer cell lines and in non-cancerous cells. For this purpose, intestinal adenocarcinoma CaCo2 cells were used. Human fibroblasts (periodontal ligament) and a primary culture of rat hepatocytes served as models of non-cancerous cells. The results showed that the sole essential oil from M. rubra has a strong prooxidative effect in cancer cells while it acts as a mild antioxidant in hepatocytes. Combined with doxorubicin, the essential oil enhanced the antiproliferative and prooxidative effects of doxorubicin in cancer cells. At higher concentrations, synergism of doxorubicin and essential oil from M. rubra was proved. In non-cancerous cells, the essential oil did not affect the toxicity of doxorubicin and the doxorubicin-mediated reactive oxygen species formation. The essential oil increased the intracellular concentration of doxorubicin and enhanced selectively the doxorubicin accumulation in nuclei of cancer cells. Taken together, essential oil from M. rubra leaves could be able to improve the doxorubicin efficacy in cancer cells due to an increased reactive oxygen species production, and the doxorubicin accumulation in nuclei of cancer cells. Georg Thieme Verlag KG Stuttgart · New York.

  2. Minoxidil (Mx) as a prophylaxis of doxorubicin--induced alopecia.

    Science.gov (United States)

    Rodriguez, R; Machiavelli, M; Leone, B; Romero, A; Cuevas, M A; Langhi, M; Romero Acuña, L; Romero Acuña, J; Amato, S; Barbieri, M

    1994-10-01

    Minoxidil (Mx) is known to induce hair growth in men with male-pattern baldness. Based on this potential, the effectiveness of Mx 2% topical solution was evaluated in cancer patients (pts) to prevent doxorubicin-induced alopecia. 48 female pts with different types of solid tumors treated with doxorubicin-based chemotherapy in a dose range of 50-60 mg/m2/cycle were randomly assigned to receive Mx 2% topical solution or placebo. 88% and 92% of pts in both arms showed severe alopecia (p = ns). No adverse effects were observed. In this study Mx 2% topical solution was non-toxic but was not effective in the prevention of chemotherapy-induced alopecia.

  3. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin.

    Directory of Open Access Journals (Sweden)

    Stephanie Morgan

    Full Text Available Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature ovarian failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin and doxorubicin were added to a mouse ovary culture system, to compare the sequence of events that leads to germ cell loss. The ability of imatinib mesylate to protect the ovary against cisplatin or doxorubicin-induced ovarian damage was also examined.Newborn mouse ovaries were cultured for a total of six days, exposed to a chemotherapeutic agent on the second day: this allowed for the examination of the earliest stages of follicle development. Cleaved PARP and TUNEL were used to assess apoptosis following drug treatment. Imatinib was added to cultures with cisplatin and doxorubicin to determine any protective effect.Histological analysis of ovaries treated with cisplatin showed oocyte-specific damage; in comparison doxorubicin preferentially caused damage to the granulosa cells. Cleaved PARP expression significantly increased for cisplatin (16 fold, p<0.001 and doxorubicin (3 fold, p<0.01. TUNEL staining gave little evidence of primordial follicle damage with either drug. Imatinib had a significant protective effect against cisplatin-induced follicle damage (p<0.01 but not against doxorubicin treatment.Cisplatin and doxorubicin both induced ovarian damage, but in a markedly different pattern, with imatinib protecting the ovary against damage by cisplatin but not doxorubicin. Any treatment designed to block the effects of chemotherapeutic agents on the ovary may need to be specific to the drug(s the patient is exposed to.

  4. Antitumor activity of doxorubicine-loaded nanoemulsion against ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights ... Keywords: Doxorubicine, Anti-tumor activity, Mean survival time, Heart histology, Nanoemulsion, Lipid profile .... the standard kit methods using fully Automated ..... effects of this new formulation in human patients.

  5. Micellar solubilization in strongly interacting binary surfactant systems. [Binary surfactant systems of: dodecyltrimethylammonium chloride + sodium dodecyl sulfate; benzyldimethyltetradecylammonium chloride + tetradecyltrimethylammonium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Treiner, C. (Universite Pierre et Marie Curie, Paris (France)); Nortz, M.; Vaution, C. (Faculte de Pharmacie de Paris-sud, Chatenay-Malabry (France))

    1990-07-01

    The apparent partition coefficient P of barbituric acids between micelles and water has been determined in mixed binary surfactant solutions from solubility measurements in the whole micellar composition range. The binary systems chosen ranged from the strongly interacting system dodecyltrimethylammonium chloride + sodium dodecyl sulfate to weakly interacting systems such as benzyldimethyltetradecylammonium chloride + tetradecyltrimethyammonium chloride. In all cases studied, mixed micelle formation is unfavorable to micellar solubilization. A correlation is found between the unlike surfactants interaction energy, as measured by the regular solution parameter {beta} and the solute partition coefficient change upon surfactant mixing. By use of literature data on micellar solubilization in binary surfactant solutions, it is shown that the change of P for solutes which are solubilized by surface adsorption is generally governed by the sign and amplitude of the interaction parameter {beta}.

  6. Extensive preclinical investigation of polymersomal formulation of doxorubicin versus Doxil-mimic formulation.

    Science.gov (United States)

    Alibolandi, Mona; Abnous, Khalil; Mohammadi, Marzieh; Hadizadeh, Farzin; Sadeghi, Fatemeh; Taghavi, Sahar; Jaafari, Mahmoud Reza; Ramezani, Mohammad

    2017-10-28

    Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects. The new formulation of the doxorubicin, synthesized previously by our group was extensively examined in the current study. This new formulation is doxorubicin encapsulated in PEG-PLGA polymersomes (PolyDOX). The main aim of the study was to compare the distribution and treatment efficacy of a new doxorubicin-polymersomal formulation (PolyDOX) with regular liposomal formulation (Doxil-mimic) in murine colon adenocarcinoma model. Additionally, the pathological, hematological changes, pharmacodynamics, biodistribution, tolerated dose and survival rate in vivo were evaluated and compared. Murine colon cancer model was induced by subcutaneous inoculation of BALB/c mice with C26 cells. Afterwards, either Doxil-mimic or PolyDOX was administered intravenously. The obtained results from biodistribution study showed a remarkable difference in the distribution of drugs in murine organs. In this regard, Doxil-mimic exhibited prolonged (48h) presence within liver tissues while PolyDOX preferentially accumulate in tumor and the presence in liver 48h post-treatment was significantly lower than that of Doxil-mimic. Obtained results demonstrated comparable final length of life for mice receiving either Doxil-mimic or PolyDOX formulations whereas tolerated dose of mice receiving Doxil-mimic was remarkably higher than those receiving PolyDOX. Therapeutic efficacy of formulation in term of tumor growth rate

  7. Circumvention of acquired resistance to doxorubicin in K562 human leukemia cells by oxatomide.

    Science.gov (United States)

    Ishikawa, M; Fujita, R; Furusawa, S; Takayanagi, M; Sasaki, K; Satoh, S

    2001-10-01

    We studied the effect of oxatomide, an antiallergic drug, on the resistance of K562 cells to doxorubicin. Oxatomide synergistically potentiated the cytotoxicity of doxorubicin in doxorubicin-resistant K562 cells (K562/DXR) at a concentration of 1-10 microM, but had hardly any synergistic effect on the parental cell line (K562) at the same concentration. Oxatomide inhibit P-glycoprotein pump-efflux activity and the binding of [3H]-azidopine to the cell-surface protein P-glycoprotein, in a dose-related manner. These results indicate that oxatomide reverses the multidrug-resistance phenotype through direct interaction with P-glycoprotein.

  8. Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser.

    Science.gov (United States)

    Ghannam, Magdy M; El Gebaly, Reem; Fadel, Maha

    2016-04-05

    The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also studied. The results indicated that lyophilization of the prepared liposomes encapsulating doxorubicin led to marked stability when stored at 5 °C and it is possible to use the re-hydrated lyophilized liposomes within 12 days post reconstitution. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells is a promising method in cancer therapy. We can conclude that lyophilization of the liposomes encapsulating doxorubicin lead to marked stability for the liposomes when stored at 5 °C. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells through the use of photosensitive sterically stabilized liposomes loaded with doxorubicin is a promising method. It proved to be applicable and successful for treatment of Ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin.

  9. High-Performance Liquid Chromatography (HPLC) Quantification of Liposome-Delivered Doxorubicin in Arthritic Joints of Collagen-Induced Arthritis Rats.

    Science.gov (United States)

    Niu, Hongqing; Xu, Menghua; Li, Shuangtian; Chen, Junwei; Luo, Jing; Zhao, Xiangcong; Gao, Chong; Li, Xiaofeng

    2017-04-14

    BACKGROUND Neoangiogenesis occurring in inflamed articular synovium in early rheumatoid arthritis (RA) is characterized by enhanced vascular permeability that allows nanoparticle agents, including liposomes, to deliver encapsulated drugs to arthritic joints and subsequently improve therapeutic efficacy and reduce adverse effects. However, the targeting distribution of liposomes in arthritic joints during RA has not been quantitatively demonstrated. We performed this study to evaluate the targeting distribution of PEGylated doxorubicin liposomes in the arthritic joints of collagen-induced arthritis (CIA) rats by high-performance liquid chromatography (HPLC). MATERIAL AND METHODS Two doxorubicin formulations were administered to CIA rats via tail intravenous injection at a single dose (50 mg/m²). CIA rats were sacrificed and the tissues of the inflamed ankle joints were collected. The content of doxorubicin in the arthritic joints was analyzed by a validated and reproducible HPLC method. A two-way ANOVA for 2×5 factorial design was used for statistical analysis. RESULTS The developed HPLC method was sensitive, precise, and reproducible. The method was successfully applied to quantify doxorubicin content in arthritic tissues. At each time point (6, 12, 24, 48, and 72 h), doxorubicin content in the arthritic joints of the doxorubicin liposome group (DOX-LIP group) was higher than in the free doxorubicin group (DOX group) (P<0.05). In the DOX-LIP group, doxorubicin levels in the arthritic joints increased gradually and significantly in the interval of 6-72 h post-administration. CONCLUSIONS PEGylated doxorubicin liposomes were targeted to, accumulated, and retained in the arthritic joints of CIA rats. The present study indicates that liposome encapsulation increases the therapeutic efficacy of antirheumatic drugs, presenting a promising therapeutic strategy for RA.

  10. Simultaneous hyperthermia and doxorubicin delivery from polymer-coated magnetite nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, G.R., E-mail: iglesias@ugr.es [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Delgado, A.V.; González-Caballero, F. [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Ramos-Tejada, M.M. [Department of Physics, University of Jaén, Linares 23700 (Spain)

    2017-06-01

    In this work, the hyperthermia response, (i.e., heating induced by an externally applied alternating magnetic field) and the simultaneous release of an anti-cancer drug (doxorubicin) by polymer-coated magnetite nanoparticles have been investigated. After describing the setup for hyperthermia measurements in suspensions of magnetic nanoparticles, the hyperthermia (represented by the rate of suspension heating and, ultimately, by the specific absorption rate or SAR) of magnetite nanoparticles (both bare and polymer-coated as drug nanocarriers) is discussed. The effect of the applied ac magnetic field on doxorubicin release is also studied, and it is concluded that the field does not interfere with the release process, demonstrating the double functionality of the investigated particles. - Highlights: • Magnetite NPs coated with polymers are used for drug delivery and hyperthermia. • The SAR of polyelectrolyte-coated NPs is larger because of their improved stability. • The antitumor drug doxorubicin is adsorbed on the coated particles. • The release rate of the drug is not affected by the ac magnetic field used in hyperthermia.

  11. Infusion volume control and calculation using metronome and drop counter based intravenous infusion therapy helper.

    Science.gov (United States)

    Park, Kyungnam; Lee, Jangyoung; Kim, Soo-Young; Kim, Jinwoo; Kim, Insoo; Choi, Seung Pill; Jeong, Sikyung; Hong, Sungyoup

    2013-06-01

    This study assessed the method of fluid infusion control using an IntraVenous Infusion Controller (IVIC). Four methods of infusion control (dial flow controller, IV set without correction, IV set with correction and IVIC correction) were used to measure the volume of each technique at two infusion rates. The infused fluid volume with a dial flow controller was significantly larger than other methods. The infused fluid volume was significantly smaller with an IV set without correction over time. Regarding the concordance correlation coefficient (CCC) of infused fluid volume in relation to a target volume, IVIC correction was shown to have the highest level of agreement. The flow rate measured in check mode showed a good agreement with the volume of collected fluid after passing through the IV system. Thus, an IVIC could assist in providing an accurate infusion control. © 2013 Wiley Publishing Asia Pty Ltd.

  12. Kaposi's sarcoma: Good outcome with doxorubicin, bleomycin and ...

    African Journals Online (AJOL)

    KS) in children in low-income countries. We prospectively treated 12 patients with an institutional review board-approved protocol consisting of four monthly courses of doxorubicin (Adriamycin), bleomycin and vincristine sulphate (ABV), with ...

  13. Spatiotemporal Control of Doxorubicin Delivery from “Stealth-Like” Prodrug Micelles

    Science.gov (United States)

    Kong, Li; Schneider, Gregory F.; Campbell, Frederick

    2017-01-01

    In the treatment of cancer, targeting of anticancer drugs to the tumor microenvironment is highly desirable. Not only does this imply accurate tumor targeting but also minimal drug release en route to the tumor and maximal drug release once there. Here we describe high-loading, “stealth-like” doxorubicin micelles as a pro-drug delivery system, which upon light activation, leads to burst-like doxorbicin release. Through this approach, we show precise spatiotemporal control of doxorubicin delivery to cells in vitro. PMID:28937592

  14. Activity of trypsin-like enzymes and gelatinases in rats with doxorubicin cardiomyopathy

    OpenAIRE

    Iu. А. Gordiienko; Ya. V. Babets; А. О. Kulinich; А. І. Shevtsova; G. О. Ushakova

    2014-01-01

    Activity of trypsin-like enzymes (ATLE) and gelatinases A and B were studied in the blood plasma and extracts from cardiac muscle, cerebral cortex and cerebellum of rats with cardiomyopathy caused by anthracycline antibiotic doxorubicin against the background of preventive application of corvitin and α-ketoglutarate. ATLE significantly increased in blood plasma and extracts from cerebral cortex but decreased in extracts from cardiac muscle and cerebellum in doxorubicin cardiomyopathy (DCMP). ...

  15. Mixtures of lecithin and bile salt can form highly viscous wormlike micellar solutions in water.

    Science.gov (United States)

    Cheng, Chih-Yang; Oh, Hyuntaek; Wang, Ting-Yu; Raghavan, Srinivasa R; Tung, Shih-Huang

    2014-09-02

    The self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Previous studies on lecithin-bile salt mixtures have reported the formation of short, rodlike micelles. Here, we show that lecithin-bile salt micelles can be further induced to grow into long, flexible wormlike structures. The formation of long worms and their resultant entanglement into transient networks is reflected in the rheology: the fluids become viscoelastic and exhibit Maxwellian behavior, and their zero-shear viscosity can be up to a 1000-fold higher than that of water. The presence of worms is further confirmed by data from small-angle neutron and X-ray scattering and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin, which suggests a strong binding interaction between the two species. In addition, micellar growth also requires a sufficient concentration of background electrolyte such as NaCl or sodium citrate that serves to screen the electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We postulate a mechanism based on changes in the molecular geometry caused by bile salts and electrolytes to explain the micellar growth.

  16. Can neutral analytes be concentrated by transient isotachophoresis in micellar electrokinetic chromatography and how much?

    Science.gov (United States)

    Matczuk, Magdalena; Foteeva, Lidia S; Jarosz, Maciej; Galanski, Markus; Keppler, Bernhard K; Hirokawa, Takeshi; Timerbaev, Andrei R

    2014-06-06

    Transient isotachophoresis (tITP) is a versatile sample preconcentration technique that uses ITP to focus electrically charged analytes at the initial stage of CE analysis. However, according to the ruling principle of tITP, uncharged analytes are beyond its capacity while being separated and detected by micellar electrokinetic chromatography (MEKC). On the other hand, when these are charged micelles that undergo the tITP focusing, one can anticipate the concentration effect, resulting from the formation of transient micellar stack at moving sample/background electrolyte (BGE) boundary, which increasingly accumulates the analytes. This work expands the enrichment potential of tITP for MEKC by demonstrating the quantitative analysis of uncharged metal-based drugs from highly saline samples and introducing to the BGE solution anionic surfactants and buffer (terminating) co-ions of different mobility and concentration to optimize performance. Metallodrugs of assorted lipophilicity were chosen so as to explore whether their varying affinity toward micelles plays the role. In addition to altering the sample and BGE composition, optimization of the detection capability was achieved due to fine-tuning operational variables such as sample volume, separation voltage and pressure, etc. The results of optimization trials shed light on the mechanism of micellar tITP and render effective determination of selected drugs in human urine, with practical limits of detection using conventional UV detector. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Hypothalamic energy metabolism is impaired by doxorubicin independently of inflammation in non-tumour-bearing rats.

    Science.gov (United States)

    Antunes, Barbara M M; Lira, Fabio Santos; Pimentel, Gustavo Duarte; Rosa Neto, José Cesar; Esteves, Andrea Maculano; Oyama, Lila Missae; de Souza, Cláudio Teodoro; Gonçalves, Cinara Ludvig; Streck, Emilio Luiz; Rodrigues, Bruno; dos Santos, Ronaldo Vagner; de Mello, Marco Túlio

    2015-08-01

    We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1β, IL-6, IL-10, TNF-α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothalamus. The DOXO group exhibited a decreased body weight (p hypothalamus is a central organ that regulates a great number of functions, such as food intake, temperature and energy expenditure, among others. Doxorubicin can lead to deep anorexia and metabolic chaos; thus, we observed the effect of this chemotherapeutic drug on the inflammation and metabolism in rats after the administration of doxorubicin in order to understand the central effect in the hypothalamus. Drug treatment by doxorubicin is used as a cancer therapy; however the use of this drug may cause harmful alterations to the metabolism. Thus, further investigations are needed on the impact of drug therapy over the long term. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Thermo-sensitive liposomes loaded with doxorubicin and lysine modified single-walled carbon nanotubes as tumor-targeting drug delivery system.

    Science.gov (United States)

    Zhu, Xiali; Xie, Yingxia; Zhang, Yingjie; Huang, Heqing; Huang, Shengnan; Hou, Lin; Zhang, Huijuan; Li, Zhi; Shi, Jinjin; Zhang, Zhenzhong

    2014-11-01

    This report focuses on the thermo-sensitive liposomes loaded with doxorubicin and lysine-modified single-walled carbon nanotube drug delivery system, which was designed to enhance the anti-tumor effect and reduce the side effects of doxorubicin. Doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes was prepared by reverse-phase evaporation method, the mean particle size was 232.0 ± 5.6 nm, and drug entrapment efficiency was 86.5 ± 3.7%. The drug release test showed that doxorubicin released more quickly at 42℃ than at 37℃. Compared with free doxorubicin, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes could efficiently cross the cell membranes and afford higher anti-tumor efficacy on the human hepatic carcinoma cell line (SMMC-7721) cells in vitro. For in vivo experiments, the relative tumor volumes of the sarcomaia 180-bearing mice in thermo-sensitive liposomes group and doxorubicin group were significantly smaller than those of N.S. group. Meanwhile, the combination of near-infrared laser irradiation at 808 nm significantly enhanced the tumor growth inhibition both on SMMC-7721 cells and the sarcomaia 180-bearing mice. The quality of life such as body weight, mental state, food and water intake of sarcomaia 180 tumor-bearing mice treated with doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes were much higher than those treated with doxorubicin. In conclusion, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes combined with near-infrared laser irradiation at 808 nm may potentially provide viable clinical strategies for targeting delivery of anti-cancer drugs. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. Effect of the hydrophilic block length on the surface-active and micellar thermodynamic properties of oxyethylene-oxybutylene diblock copolymers in aqueous solution

    International Nuclear Information System (INIS)

    Khan, A.; Usman, M.; Siddiq, M.; Fatima, G.; Harrison, W.

    2009-01-01

    The effect of hydrophilic block length on the surface and micellar thermodynamic properties of aqueous solution of E/sub 40/B/sub 8/, E/sub 80/B/sub 8/ and E/sub 120/B/sub 8/ diblock copolymers, were studied by surface tension measurements over a wide concentration and temperature range; where E stands for an oxyethylene unit and B for an oxybutylene unit. Like conventional surfactants, two breaks (change in the slope) were observed in the surface tension vs logarithm of concentration curve for all the three copolymers. Surface tension measurements were used to estimate surface excess concentrations (r m), area per molecule at air/water interface a and thermodynamic parameters for all adsorption of the pre-micellar region in the temperature range 20 to 50 degree C. Likewise the critical micelle concentration, CMC and thermodynamic parameters for micellization were also calculated for the post-micellar solutions at all temperatures. For comparison the thermodynamic parameters of adsorption and micellization are discussed in detail. The impact of varying E-block length and temperature on all calculated parameters are also discussed. This study shows the importance of hydrophobic-hydrophilic-balance (HHB) of copolymers on various surface and micellar properties. (author)

  20. Inflammatory mediators in a short-time mouse model of doxorubicin-induced cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Pecoraro, Michela; Del Pizzo, Mariagiovanna; Marzocco, Stefania; Sorrentino, Rosalinda [Department of Pharmacy, University of Salerno, Fisciano, SA (Italy); Ciccarelli, Michele; Iaccarino, Guido [Department of Medicine and Surgery, University of Salerno, Baronissi, SA (Italy); Pinto, Aldo [Department of Pharmacy, University of Salerno, Fisciano, SA (Italy); Popolo, Ada, E-mail: apopolo@unisa.it [Department of Pharmacy, University of Salerno, Fisciano, SA (Italy)

    2016-02-15

    Doxorubicin (DOXO) is commonly used to treat a wide range of malignant tumors, but its clinical use is limited by acute and chronic cardiotoxicity. The precise mechanism underlying DOXO-induced cardiotoxicity is still not completely elucidated, but cardiac inflammation seems to be involved. Effects of DOXO on proinflammatory cytokines, inflammatory cell infiltration, and necrosis have been proven only when a functional impairment has already occurred, so this study aimed to investigate the acute effect of DOXO administration in mouse heart. The results of our study demonstrated alterations in cardiac function parameters assessed by ultrasound within 24 h after a single injection of DOXO, with a cumulative effect along the increase of the dose and the number of DOXO administrations. At the same time, DOXO causes a significant production of proinflammatory cytokines (such as TNF-α and IL-6) with a concomitant reduction of IL-10, a well-known antiinflammatory cytokine. Furthermore, overexpression of inducible nitric oxide synthase (iNOS) in heart tissue and increased levels of serum nitrite in DOXO-treated mice were detected. Notably, DOXO administration significantly increased nitrotyrosine expression in mouse heart. Our data support the hypothesis that these early events, could be responsible for the later onset of more severe deleterious remodeling leading to DOXO induced cardiomyopathy. - Highlights: • Doxorubicin induces echocardiographic alterations of the main cardiac functional parameters. • Doxorubicin induces increase of TNF-α and IL-6 production and iNOS expression. • Doxorubicin causes a significant reduction of the antiinflammatory cytokine IL-10. • The doses are lower than that used in human. • Doxorubicin administration significantly increased nitrotyrosine expression.

  1. Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancer xenografts

    International Nuclear Information System (INIS)

    El-Zawahry, Ahmed; McKillop, John; Voelkel-Johnson, Christina

    2005-01-01

    Prostate cancer is a significant health problem among American men. Treatment strategies for androgen-independent cancer are currently not available. Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a death receptor ligand that can induce apoptosis in a variety of cancer cell lines, including androgen-independent PC3 prostate carcinoma cells. In vitro, TRAIL-mediated apoptosis of prostate cancer cell lines can be enhanced by doxorubicin and correlates with the downregulation of the anti-apoptotic protein c-FLIP. This study evaluated the effects of doxorubicin on c-FLIP expression and tumor growth in combination with Apo2L/TRAIL in a xenograft model. In vitro cytotoxic effects of TRAIL were measured using a MTS-based viability assay. For in vivo studies, PC3 prostate carcinoma cells were grown subcutaneously in athymic nude mice and tumor growth was measured following treatment with doxorubicin and/or Apo2L/TRAIL. c-FLIP expression was determined by western blot analysis. Apoptosis in xenografts was detected using TUNEL. Statistical analysis was performed using the student t-test. In vitro experiments show that PC3 cells are partially susceptible to Apo2L/TRAIL and that susceptibility is enhanced by doxorubicin. In mice, doxorubicin did not significantly affect the growth of PC3 xenografts but reduced c-FLIP expression in tumors. Expression of c-FLIP in mouse heart was decreased only at the high doxorubicin concentration (8 mg/kg). Combination of doxorubicin with Apo2L/TRAIL resulted in more apoptotic cell death and tumor growth inhibition than Apo2L/TRAIL alone. Combination of doxorubicin and Apo2L/TRAIL is more effective in growth inhibition of PC3 xenografts in vivo than either agent alone and could present a novel treatment strategy against hormone-refractory prostate cancer. The intracellular mechanism by which doxorubicin enhances the effect of Apo2L/TRAIL on PC3 xenografts may be by reducing expression of c-FLIP

  2. Tween 20 increases intestinal transport of doxorubicin in vitro but not in vivo

    DEFF Research Database (Denmark)

    Al-Sharaf, Amal; Holm, Rene; Nielsen, Carsten Uhd

    2016-01-01

    co-administered with P-gp inhibitors (non-ionic surfactants) in vitro and in vivo . The aim of the present study was thus to investigate if different non-ionic surfactants would have a similar effect on the in vitro and in vivo absorption of doxorubicin. This was investigated in vitro in Caco-2 cells...... and by oral co-administration of doxorubicin together with tween 20 to male Sprague Dawley rats. 200 μM (0.025%) tween 20 increased the intestinal absorptive permeability of doxorubicin in vitro by 48 ± 4% from 8.8 × 10(-6)cm/s to 13.0 × 10(-6)cm/s. Further, the efflux ratio was reduced from 2.2 ± 0.06 to 1.2...

  3. The role of Nardostachys jatamansi against doxorubicin-induced ...

    African Journals Online (AJOL)

    SUBASHINI

    2013-12-04

    Dec 4, 2013 ... Key words: Nardostachys jatamansi, doxorubicin, cytokine, glutathione, .... hoc test LSD, *P < 0.05, (Comparisons: control vs DOX induced group; DOX induced group vs NJ ... Figure 2 A-D shows the histological pictures of the.

  4. Interactions between 9,10-anthraquinone and aromatic amines in homogeneous and micellar media: A laser flash photolysis and magnetic field effect study

    International Nuclear Information System (INIS)

    Chowdhury, Adity; Basu, Samita

    2006-01-01

    The interactions between 9,10-anthraquinone (AQ) and different aromatic amines, N,N-dimethylaniline and 4,4'-bis (dimethylamino) diphenylmethane (DMDPM), have been studied using absorption, steady-state fluorescence, and laser flash photolysis techniques in organic homogeneous and heterogeneous micellar media. In polar organic homogeneous medium, electron transfer (ET) occurs from amines to excited AQ. In micellar medium, similar intermolecular ET is observed. However, in latter medium, ET predominates over hydrogen abstraction from micelles by excited AQ itself. The occurrence of ET has been further supported by the application of an external magnetic field during laser flash photolysis experiments, which modulates the yield of radical ion pairs formed through ET. Another novel feature, which has also been discussed here, is the abnormal behavior of DMDPM in micellar medium pertaining to energy transfer

  5. A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors.

    Science.gov (United States)

    Schelman, William R; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M; Ivy, Percy; Wilding, George; Traynor, Anne M

    2009-05-01

    To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin. Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

  6. The Mobile Phase Motion in Ascending Micellar Thin-Layer Chromatography with Normal-Phase Plates

    NARCIS (Netherlands)

    Boichenko, Alexander P.; Makhno, Iryna V.; Renkevich, Anton Yu.; Loginova, Lidia P.

    2011-01-01

    The physical chemical characteristics (surface tension and viscosity) of micellar mobile phases based on the cationic surfactant cetylpiridinium chloride and additives of alcohols (ethanol, 1-propanol, 1-butanol, 1-pentanol) have been obtained in this work. The effect of mobile phase properties on

  7. Atmospheric pressure photoionization for enhanced compatibility in on-line micellar electrokinetic chromatography-mass spectrometry

    NARCIS (Netherlands)

    Mol, Roelof; De Jong, Gerhardus J.; Somsen, Govert W.

    2005-01-01

    Atmospheric pressure photoionization (APPI) is presented as a novel means for the combination of micellar electrokinetic chromatography (MEKC) and mass spectrometry (MS). The on-line coupling is achieved using an adapted sheath flow interface installed on an orthogonal APPI source. Acetone or

  8. Organisation and shape of micellar solutions of block copolymers

    Science.gov (United States)

    Gaspard, J. P.; Creutz, S.; Bouchat, Ph.; Jérôme, R.; Cohen Stuart, M.

    1997-02-01

    Diblock copolymers of polymethacrylic acid sodium salt, forming the hair, and styrene derivatives have been studied in aqueous solutions by SANS and SAXS. The influence of both the chemical nature and the length of the hydrophobic bloxk on the size and shape of micelles have been investigated. The micellar core size is in agreement with the theoretical evaluation for copolymers with a short hydrophobic sequence. In contrast, in case of larger hydrophobic blocks, the measured size is incompatible with a star-like model. Various hypotheses are presented for the latter.

  9. The effect of vorinostat on the development of resistance to doxorubicin in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Timothy B Lautz

    Full Text Available Histone deacetylase (HDAC inhibitors, especially vorinostat, are currently under investigation as potential adjuncts in the treatment of neuroblastoma. The effect of vorinostat co-treatment on the development of resistance to other chemotherapeutic agents is unknown. In the present study, we treated two human neuroblastoma cell lines [SK-N-SH and SK-N-Be(2C] with progressively increasing doses of doxorubicin under two conditions: with and without vorinsotat co-therapy. The resultant doxorubicin-resistant (DoxR and vorinostat-treated doxorubicin resistant (DoxR-v cells were equally resistant to doxorubicin despite significantly lower P-glycoprotein expression in the DoxR-v cells. Whole genome analysis was performed using the Ilumina Human HT-12 v4 Expression Beadchip to identify genes with differential expression unique to the DoxR-v cells. We uncovered a number of genes whose differential expression in the DoxR-v cells might contribute to their resistant phenotype, including hypoxia inducible factor-2. Finally, we used Gene Ontology to categorize the biological functions of the differentially expressed genes unique to the DoxR-v cells and found that genes involved in cellular metabolism were especially affected.

  10. Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

    Science.gov (United States)

    Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

    2017-12-01

    Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

  11. Iron distribution in cancer cells following doxorubicin exposure using proton and X-ray synchrotron radiation microprobes

    International Nuclear Information System (INIS)

    Ortega, R.; Deves, G.; Bohic, S.; Simionovici, A.; Menez, B.; Bonnin-Mosbah, M.

    2001-01-01

    Chemical studies have shown that doxorubicin, a well-established anticancer agent, is a powerful iron chelator and the resultant iron-drug complex is an efficient catalyst of the conversion of hydrogen peroxide to the highly reactive hydroxyl radical. However, the intracellular complexation of doxorubicin with iron is still debated. Using nuclear microprobe analysis (NMPA), we previously observed in human ovarian cancer cells exposed to 20 μM iodo-doxorubicin (IDX) that iodine and iron cellular distributions were spatially correlated, suggesting a mechanism of intracellular iron chelation by the anthracycline compound. Because maximal plasma drug concentrations in patients are expected to be around 5 μM, NMPA and X-ray absorption near edge spectroscopy (XANES) experiments for iron speciation analysis were performed on cultured cells exposed to pharmacological doses of 2 μM IDX or doxorubicin

  12. miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1

    Directory of Open Access Journals (Sweden)

    Jingpei Long

    2015-01-01

    Full Text Available MicroRNAs (miRNAs family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of doxorubicin resistance is a common and critical limitation to cancer therapy. The aim of this study was to investigate whether miR-193b mediated the resistance of breast cancer cells to doxorubicin by targeting myeloid cell leukemia-1 (MCL-1. In this study, we found that miR-193b levels were significantly lower in doxorubicin-resistant MCF-7 (MCF-7/DOXR cells than in the parental MCF-7 cells. We observed that exogenous miR-193b significantly suppressed the ability of MCF-7/DOXR cells to resist doxorubicin. It demonstrated that miR-193b directly targeted MCL-1 3′-UTR (3′-Untranslated Regions. Further studies indicated that miR-193b sensitized MCF-7/DOXR cells to doxorubicin through a mechanism involving the downregulation of MCL-1. Together, our findings provide evidence that the modulation of miR-193b may represent a novel therapeutic target for the treatment of breast cancer.

  13. Anti-cancer effect of oncolytic adenovirus-armed shRNA targeting MYCN gene on doxorubicin-resistant neuroblastoma cells.

    Science.gov (United States)

    Li, Yuan; Zhuo, Baobiao; Yin, Yiyu; Han, Tao; Li, Shixian; Li, Zhengwei; Wang, Jian

    2017-09-09

    Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma. Here we further report ZD55-shMYCN re-sensitized doxorubicin-resistant cells to doxorubicin (as shown by reduced proliferation, increased apoptosis, and inhibited cell migration), and reduced the in vivo growth rate of neuroblastoma xenografts by down-regulation of MRP expression. Sequential therapy with doxorubicin did not affect the replication of ZD55-shMYCN in doxorubicin-resistant neuroblastoma cells, but decreased the expression of Bcl-2, Bcl-X L , MMP-1. Thus, this synergistic effect of ZD55-shMYCN in combination with doxorubicin provides a novel therapy strategy for doxorubicin-resistant neuroblastoma, and is a promising approach for further clinical development. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Toxicity of Doxorubicin on Pig Liver After Chemoembolization with Doxorubicin-loaded Microspheres: A Pilot DNA-microarrays and Histology Study

    Energy Technology Data Exchange (ETDEWEB)

    Verret, Valentin, E-mail: valentin.verret@archimmed.com; Namur, Julien; Ghegediban, Saieda Homayra [ArchimMed (France); Wassef, Michel [University of Paris 7-Denis Diderot, Department of Pathology, Faculty of Medicine, AP-HP Hopital Lariboisiere (France); Moine, Laurence [Universite Paris Sud, Faculte de Pharmacie, UMR CNRS 8612, IFR 141-ITFM (France); Bonneau, Michel [AP-HP/INRA, Centre de Recherche En Imagerie Interventionnelle (France); Pelage, Jean-Pierre [AP-HP Hopital Ambroise Pare, Department of Interventional Radiology (France); Laurent, Alexandre [AP-HP/INRA, Centre de Recherche En Imagerie Interventionnelle (France)

    2013-02-15

    The potential mechanisms accounting for the hepatotoxicity of doxorubicin-loaded microspheres in chemoembolization were examined by combining histology and DNA-microarray techniques.The left hepatic arteries of two pigs were embolized with 1 mL of doxorubicin-loaded (25 mg; (DoxMS)) or non-loaded (BlandMS) microspheres. The histopathological effects of the embolization were analyzed at 1 week. RNAs extracted from both the embolized and control liver areas were hybridized onto Agilent porcine microarrays. Genes showing significantly different expression (p < 0.01; fold-change > 2) between two groups were classified by biological process. At 1 week after embolization, DoxMS caused arterial and parenchymal necrosis in 51 and 38 % of embolized vessels, respectively. By contrast, BlandMS did not cause any tissue damage. Up-regulated genes following embolization with DoxMS (vs. BlandMS, n = 353) were mainly involved in cell death, apoptosis, and metabolism of doxorubicin. Down-regulated genes (n = 120) were mainly related to hepatic functions, including enzymes of lipid and carbohydrate metabolisms. Up-regulated genes included genes related to cell proliferation (growth factors and transcription factors), tissue remodeling (MMPs and several collagen types), inflammatory reaction (interleukins and chemokines), and angiogenesis (angiogenic factors and HIF1a pathway), all of which play an important role in liver healing and regeneration. DoxMS caused lesions to the liver, provoked cell death, and disturbed liver metabolism. An inflammatory repair process with cell proliferation, tissue remodeling, and angiogenesis was rapidly initiated during the first week after chemoembolization. This pilot study provides a comprehensive method to compare different types of DoxMS in healthy animals or tumor models.

  15. Reverting doxorubicin resistance in colon cancer by targeting a key signaling protein, steroid receptor coactivator.

    Science.gov (United States)

    Xiong, Sang; Xiao, Gong-Wei

    2018-04-01

    Although there have been notable improvements in treatments against cancer, further research is required. In colon cancer, nearly all patients eventually experience drug resistance and stop responding to the approved drugs, making treatment difficult. Steroid receptor coactivator (SRC) is an oncogenic nuclear receptor coactivator that serves an important role in drug resistance. The present study generated a doxorubicin-resistant colon cancer cell line, in which the upregulation/activation of SRC was responsible for drug resistance, which in turn activated AKT. Overexpression of receptor tyrosine kinase-like epidermal growth factor receptor and insulin-like growth factor 1 receptor also induced SRC expression. It was observed that doxorubicin resistance in colon cancer also induced epithelial to mesenchymal transition, a decrease in expression of epithelial marker E-cadherin and an increase in the expression of mesenchymal markers, including N-cadherin and vimentin. Additionally, the present study indicated that SRC acts as a common signaling node, and inhibiting SRC in combination with doxorubicin treatment in doxorubicin-resistant cells aids in reversing the resistance. Thus, the present study suggests that activation of SRC is responsible for doxorubicin resistance in colon cancer. However, further research is required to understand the complete mechanism of how drug resistance occurs and how it may be tackled to treat patients.

  16. Muscular pseudotumor of the breast following doxorubicin and radiation therapy for oat cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Wergowske, G.; Chang, J.C.; Marger, D.

    1982-01-01

    Two male patients developed muscular pseudotumor of the breast following combined treatment of radiation and chemotherapy with cyclophosphamide, doxorubicin, methotrexate and procarbazine for oat cell carcinoma of the lung. The pathologic findings of the biopsy specimens revealed muscle and capillary changes similar to previously reported myocardiotoxicity from doxorubicin and radiation therapy. Discussed is a possible additive or synergistic toxic effect of doxorubicin and radiation therapy in the development of muscular pseudotumor of the breast

  17. Effect of micellar collisions and polyvinylpyrrolidone confinement on the electrical conductivity percolation parameters of water/AOT/isooctane reverse micelles

    Science.gov (United States)

    Guettari, Moez; Aferni, Ahmed E. L.; Tajouri, Tahar

    2017-12-01

    The main aim of this paper is the analysis of micellar collisions and polymer confinement effects on the electrical conductivity percolative behavior of water/sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/isooctane reverse micelles. Firstly, we have performed conductance measurements of the system for three AOT to isooctane volume ratio, φm = 0.1 , 0.15 and 0.2 to examine the influence of micellar collisions on the percolation parameters. All the measurements were carried out over the 298.15 K-333.15 K temperature range at a fixed water to AOT molar ratio, W0 = 45 . We have assessed that the rise of micellar collisions frequency enhances the conductance percolation. Secondly, the confinement effect of a water-soluble polymer, polyvinylpyrrolidone (PVP), on the reverse micelles conductance behavior was investigated. Temperature-induced percolation, Tp , have shown a dependence on the polymer concentration, CPVP . It was also observed that for various PVP concentrations, the activation energy of percolation decreases. Finally, the values of the critical exponents determined in the presence and absence of PVP prove that the polymer affects the dynamic of percolation.

  18. [The therapeutic effect of HSV1-hGM-CSF combined with doxorubicin on the mouse breast cancer model].

    Science.gov (United States)

    Zhuang, X F; Zhang, S R; Liu, B L; Wu, J L; Li, X Q; Gu, H G; Shu, Y

    2018-03-23

    Objective: To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice. Methods: We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 μg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed. Results: Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro . Doxorubicin induced the G(2)/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm(3,) (216.80±57.18)mm(3,) (246.10±21.90)mm(3,) (327.50±44.24)mm(3,) (213.30±32.31)mm(3) and (495.80±75.87)mm(3) in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo ( P CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control ( P CSF is observed in 4T1 mouse breast cancer.

  19. SANS study of three-layer micellar particles

    CERN Document Server

    Plestil, J; Kuklin, A I; Cubitt, R

    2002-01-01

    Three-layer nanoparticles were prepared by polymerization of methyl methacrylate (MMA) in aqueous micellar solutions of poly(methyl methacrylate)-block-poly(methacrylic acid) (PMMA-b-PMA) and polystyrene-block-poly(methacrylic acid) (PS-b-PMA). The resulting polymer forms a layer on the core surface of the original micelles. SANS curves were fitted using an ellipsoidal (PMMA/PMMA/PMA) or spherical (PS/PMMA/PMA) model for the particle core. The particle size (for the presented series of the PMMA/PMMA/PMA particles, the core semiaxes ranged from 87 to 187 A and the axis ratio was about 6) can be finely tuned by variation of monomer concentration. Time-resolved SANS experiments were carried out to describe the growth of the PS/PMMA/PMA particles during polymerization. (orig.)

  20. The stress granule protein Vgl1 and poly(A)-binding protein Pab1 are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Morita, Takahiro; Satoh, Ryosuke; Umeda, Nanae; Kita, Ayako; Sugiura, Reiko

    2012-01-01

    Highlights: ► Stress granules (SGs) as a mechanism of doxorubicin tolerance. ► We characterize the role of stress granules in doxorubicin tolerance. ► Deletion of components of SGs enhances doxorubicin sensitivity in fission yeast. ► Doxorubicin promotes SG formation when combined with heat shock. ► Doxorubicin regulates stress granule assembly independent of eIF2α phosphorylation. -- Abstract: Doxorubicin is an anthracycline antibiotic widely used for chemotherapy. Although doxorubicin is effective in the treatment of several cancers, including solid tumors and leukemias, the basis of its mechanism of action is not completely understood. Here, we describe the effects of doxorubicin and its relationship with stress granules formation in the fission yeast, Schizosaccharomyces pombe. We show that disruption of genes encoding the components of stress granules, including vgl1 + , which encodes a multi-KH type RNA-binding protein, and pab1 + , which encodes a poly(A)-binding protein, resulted in greater sensitivity to doxorubicin than seen in wild-type cells. Disruption of the vgl1 + and pab1 + genes did not confer sensitivity to other anti-cancer drugs such as cisplatin, 5-fluorouracil, and paclitaxel. We also showed that doxorubicin treatment promoted stress granule formation when combined with heat shock. Notably, doxorubicin treatment did not induce hyperphosphorylation of eIF2α, suggesting that doxorubicin is involved in stress granule assembly independent of eIF2α phosphorylation. Our results demonstrate the usefulness of fission yeast for elucidating the molecular targets of doxorubicin toxicity and suggest a novel drug-resistance mechanism involving stress granule assembly.

  1. Continuous-infusion adriamycin

    International Nuclear Information System (INIS)

    Benjamin, R.S.; Chawla, S.P.; Ewer, M.S.; Hortobagyi, G.N.

    1986-01-01

    This chapter discusses the diminished cardiotoxicity as well as diminished nausea and vomiting with continuous infusions of adriamycin to patients undergoing radiation therapy, particularly with infusions of 48 hours or longer, and best with 96-hour infusions, the longest duration that has been studied systematically. In breast cancer, data show that more adriamycin is better, but only for a selected subgroup of patients: those with complete remission. The diminished cardiotoxicity makes the use of adriamycin more attractive in the adjuvant situation, where increased safety will decrease the chances of long-term complications and make retreatment easy for cured patients who develop second malignancies

  2. Effect of calcium chelators on physical changes in casein micelles in concentrated micellar casein solutions

    NARCIS (Netherlands)

    Kort, de E.J.P.; Minor, M.; Snoeren, T.H.M.; Hooijdonk, van A.C.M.; Linden, van der E.

    2011-01-01

    The effect of calcium chelators on physical changes of casein micelles in concentrated micellar casein solutions was investigated by measuring calcium-ion activity, viscosity and turbidity, and performing ultracentrifugation. The highest viscosities were measured on addition of sodium

  3. siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells

    International Nuclear Information System (INIS)

    Dong, Xuejun; Liu, Anding; Zer, Cindy; Feng, Jianguo; Zhen, Zhuan; Yang, Mingfeng; Zhong, Li

    2009-01-01

    Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. Concomitant administration of doxorubicin and another cancer drug may be able to sensitize tumor cells to the cytotoxicity of doxorubicin and lowers the therapeutic dosage. In this study, we examined the combined effect of low-dose doxorubicin and siRNA inhibition of telomerase on breast cancer cells. We found that when used individually, both treatments were rapid and potent apoptosis inducers; and when the two treatments were combined, we observed an enhanced and sustained apoptosis induction in breast cancer cells. siRNA targeting the mRNA of the protein component of telomerase, the telomerase reverse transcriptase (hTERT), was transfected into two breast cancer cell lines. The siRNA inhibition was confirmed by RT-PCR and western blot on hTERT mRNA and protein levels, respectively, and by measuring the activity level of telomerase using the TRAP assay. The effect of the hTERT siRNA on the tumorigenicity of the breast cancer cells was also studied in vivo by injection of the siRNA-transfected breast cancer cells into nude mice. The effects on cell viability, apoptosis and senescence of cells treated with hTERT siRNA, doxorubicin, and the combined treatment of doxorubicin and hTERT siRNA, were examined in vitro by MTT assay, FACS and SA-β-galactosidase staining. The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. In vivo, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 μM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 μM doxorubicin killed twice as many

  4. Differential thermodynamic signature of carbon nanomaterials using amphiphilic micellar probe

    Science.gov (United States)

    Bhattacharyya, Tamoghna; Dasgupta, Anjan Kr

    2018-04-01

    The thermodynamic signature of single-wall carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs) and reduced graphene oxide (rG-O) using amphiphilic micellar probe has been explored. The study reveals an intricate correlation between nano-surface topology and calorimetric profile of SWCNTs, MWCNTs and rG-O. The critical micelle concentration (CMC) is found to be sensitive to the topological diversity of nanomaterials. The study explores a thermodynamic approach to characterize the nano-surface topology of SWCNTs, MWCNTs and graphene surface.

  5. Real time in vitro studies of doxorubicin release from PHEMA nanoparticles

    Directory of Open Access Journals (Sweden)

    Bajpai AK

    2009-10-01

    Full Text Available Abstract Background Many anticancer agents have poor water solubility and therefore the development of novel delivery systems for such molecules has received significant attention. Nanocarriers show great potential in delivering therapeutic agents into the targeted organs or cells and have recently emerged as a promising approach to cancer treatments. The aim of this study was to prepare and use poly-2-hydroxyethyl methacrylate (PHEMA nanoparticles for the controlled release of the anticancer drug doxorubicin. Results PHEMA nanoparticles have been synthesized and characterized using FTIR and scanning electron microscopy (SEM, particle size analysis and surface charge measurements. We also studied the effects of various parameters such as percent loading of drugs, chemical architecture of the nanocarriers, pH, temperature and nature of the release media on the release profiles of the drug. The chemical stability of doxorubicin in PBS was assessed at a range of pH. Conclusion Suspension polymerization of 2-hydroxyethyl methacrylate (HEMA results in the formation of swellable nanoparticles of defined composition. PHEMA nanoparticles can potentially be used for the controlled release of the anticancer drug doxorubicin.

  6. Rheological Properties of Hydrophobically Associative Copolymers Prepared in a Mixed Micellar Method Based on Methacryloxyethyl-dimethyl Cetyl Ammonium Chloride as Surfmer

    Directory of Open Access Journals (Sweden)

    Rui Liu

    2014-01-01

    Full Text Available A novel cationic surfmer, methacryloxyethyl-dimethyl cetyl ammonium chloride (DMDCC, is synthesized. The micellar properties, including critical micelle concentration and aggregation number, of DMDCC-SDS mixed micelle system are studied using conductivity measurement and a steady-state fluorescence technique. A series of water-soluble associative copolymers with acrylamide and DMDCC are prepared using the mixed micellar polymerization. Compared to conventional micellar polymerization, this new method could not only reasonably adjust the length of the hydrophobic microblock, that is, NH, but also sharply reduce the amount of surfactant. Their rheological properties related to hydrophobic microblock and stickers are studied by the combination of steady flow and linear viscoelasticity experiments. The results indicate that both the hydrophobic content and, especially the length of the hydrophobic microblock are the dominating factors effecting the intermolecular hydrophobic association. The presence of salt influences the dynamics of copolymers, resulting in the variation of solution characters. Viscosity measurement indicates that mixed micelles between the copolymer chain and SDS molecules serving as junction bridges for transitional network remarkably enhance the viscosity. Moreover, the microscopic structures of copolymers at different experimental conditions are conducted by ESEM. This method gives us an insight into the preparation of hydrophobically associative water-soluble copolymers by cationic surfmer-anionic surfactant mixed micellar polymerization with good performance.

  7. Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

    International Nuclear Information System (INIS)

    Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

    1996-01-01

    To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

  8. Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive and -Resistant Cell Lines in the Chick Embryo Model

    Directory of Open Access Journals (Sweden)

    Katarzyna Zabielska-Koczywąs

    2018-02-01

    Full Text Available Proteomic analyses are rapid and powerful tools that are used to increase the understanding of cancer pathogenesis, discover cancer biomarkers and predictive markers, and select and monitor novel targets for cancer therapy. Feline injection-site sarcomas (FISS are aggressive skin tumours with high recurrence rates, despite treatment with surgery, radiotherapy, and chemotherapy. Doxorubicin is a drug of choice for soft tissue sarcomas, including FISS. However, multidrug resistance is one of the major causes of chemotherapy failure. The main aim of the present study was to identify proteins that differentiate doxorubicin-resistant from doxorubicin-sensitive FISS using two-dimensional gel electrophoresis (2DE, followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS analysis. Using the three-dimensional (3D preclinical in ovo model, which resembles features of spontaneous fibrosarcomas, three significantly (p ≤ 0.05 differentially expressed proteins were identified in tumours grown from doxorubicin-resistant fibrosarcoma cell lines (FFS1 and FFS3 in comparison to the doxorubicin-sensitive one (FFS5: Annexin A5 (ANXA5, Annexin A3 (ANXA3, and meiosis-specific nuclear structural protein 1 (MNS1. Moreover, nine other proteins were significantly differentially expressed in tumours grown from the high doxorubicin-resistant cell line (FFS1 in comparison to sensitive one (FFS5. This study may be the first proteomic fingerprinting of FISS reported, identifying potential candidates for specific predictive biomarkers and research targets for doxorubicin-resistant FISS.

  9. Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

    International Nuclear Information System (INIS)

    Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

    1986-01-01

    Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting

  10. The stress granule protein Vgl1 and poly(A)-binding protein Pab1 are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Takahiro [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan); Satoh, Ryosuke [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Umeda, Nanae; Kita, Ayako [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan); Sugiura, Reiko, E-mail: sugiurar@phar.kindai.ac.jp [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Stress granules (SGs) as a mechanism of doxorubicin tolerance. Black-Right-Pointing-Pointer We characterize the role of stress granules in doxorubicin tolerance. Black-Right-Pointing-Pointer Deletion of components of SGs enhances doxorubicin sensitivity in fission yeast. Black-Right-Pointing-Pointer Doxorubicin promotes SG formation when combined with heat shock. Black-Right-Pointing-Pointer Doxorubicin regulates stress granule assembly independent of eIF2{alpha} phosphorylation. -- Abstract: Doxorubicin is an anthracycline antibiotic widely used for chemotherapy. Although doxorubicin is effective in the treatment of several cancers, including solid tumors and leukemias, the basis of its mechanism of action is not completely understood. Here, we describe the effects of doxorubicin and its relationship with stress granules formation in the fission yeast, Schizosaccharomyces pombe. We show that disruption of genes encoding the components of stress granules, including vgl1{sup +}, which encodes a multi-KH type RNA-binding protein, and pab1{sup +}, which encodes a poly(A)-binding protein, resulted in greater sensitivity to doxorubicin than seen in wild-type cells. Disruption of the vgl1{sup +} and pab1{sup +} genes did not confer sensitivity to other anti-cancer drugs such as cisplatin, 5-fluorouracil, and paclitaxel. We also showed that doxorubicin treatment promoted stress granule formation when combined with heat shock. Notably, doxorubicin treatment did not induce hyperphosphorylation of eIF2{alpha}, suggesting that doxorubicin is involved in stress granule assembly independent of eIF2{alpha} phosphorylation. Our results demonstrate the usefulness of fission yeast for elucidating the molecular targets of doxorubicin toxicity and suggest a novel drug-resistance mechanism involving stress granule assembly.

  11. Responsive micellar films of amphiphilic block copolymer micelles: control on micelle opening and closing.

    Science.gov (United States)

    Chen, Zhiquan; He, Changcheng; Li, Fengbin; Tong, Ling; Liao, Xingzhi; Wang, Yong

    2010-06-01

    We reported the deliberate control on the micelle opening and closing of amphiphilic polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) micellar films by exposing them to selective solvents. We first treated the micellar films with polar solvents including ethanol and water (pH = 4, 8, and 12) that have different affinities to P2VP. We observed opening of the micelles in all the cases. Both the size of opened pores and the opening rate are dependent on the solvency of different solvents for P2VP. We then explored the closing behavior of the opened micelles using solvents having different affinities to PS. We found that the opened micelles were recovered to their initial closed micelle forms. The recovery was accompanied by a slow micelle disassociation process which gradually reduced the micelle size. The rates of the micelle closing and disassociation are also dependent on the solvency of different solvents for PS.

  12. Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization.

    Science.gov (United States)

    Cao, Fengjuan; Amidon, Gordon L; Rodriguez-Hornedo, Nair; Amidon, Gregory E

    2016-03-07

    The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick's law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid-liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals.

  13. Removal of phenol from synthetic waste water using Gemini micellar-enhanced ultrafiltration (GMEUF)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenxiang [MOE Key Laboratory of Regional Energy and Environmental Systems Optimization, Resources and Environmental Research Academy, North China Electric Power University, Beijing 102206 (China); Huang, Guohe, E-mail: huang@iseis.org [MOE Key Laboratory of Regional Energy and Environmental Systems Optimization, Resources and Environmental Research Academy, North China Electric Power University, Beijing 102206 (China); Wei, Jia [Faculty of Engineering and Applied Science, University of Regina, Regina, Saskatchewan, Canada S4S 0A2 (Canada); Li, Huiqin; Zheng, Rubing; Zhou, Ya [MOE Key Laboratory of Regional Energy and Environmental Systems Optimization, Resources and Environmental Research Academy, North China Electric Power University, Beijing 102206 (China)

    2012-10-15

    Highlights: Black-Right-Pointing-Pointer Gemini surfactant micellar enhanced ultrafiltration was used to remove phenol. Black-Right-Pointing-Pointer The effect of different hydrophilic head groups of surfactant was analyzed. Black-Right-Pointing-Pointer SEM, ATR-FTIR and mercury porosimeter were applied to elucidate membrane fouling. Black-Right-Pointing-Pointer Gemini surfactant had superior performance in comparing with conventional surfactant. - Abstract: Comprehensive studies were conducted on the phenol wastewater ultrafiltration (UF) with the help of various concentrations of cationic Gemini surfactant (N1-dodecyl-N1,N1,N2,N2-tetramethyl-N2-octylethane-1,2-diaminium bromide, CG), conventional cationic surfactant (dodecyl trimethyl ammonium bromide, DTAB), anionic surfactant (sodium dodecyl sulfate, SDS) and nonionic surfactant ((dodecyloxy)polyethoxyethanol, Brij35). A flat sheet module with polyethersulfone (PES) membrane was employed in this investigation. The effects of feed concentration (phenol and surfactant) on the retention of phenol and surfactant, permeate flux and membrane fouling by micelles were evaluated. The distribution coefficient (D), the loading of the micelles (L{sub m}) and the equilibrium distribution constant (K) were also utilized to estimate the micellar-enhanced ultrafiltration ability for phenol. Scanning electron microscope (SEM), Fourier transform infrared spectrometer with attenuated total reflectance accessory (ATR-FTIR) and mercury porosimeter were applied to analyze membrane surface morphology, membrane material characteristics and membrane fouling for the original and fouled membranes. Based on the above analysis, the performance of the selected Gemini surfactant was proved superior in the following aspects: retention of phenol/surfactant (peak value is 95.8% for phenol retention), permeate flux and membrane fouling with respect to other conventional surfactants possessing equal alkyl chain length. These results demonstrated

  14. The Nature of the Micellar Stern Region As Studied by Reaction Kinetics. 2

    NARCIS (Netherlands)

    Buurma, Niklaas J.; Serena, Paola; Blandamer, Michael J.; Engberts, Jan B.F.N.

    2004-01-01

    The nature of rate-retarding effects of cationic micelles on the water-catalyzed hydrolyses of a series of para-substituted 1-benzoyl-1,2,4-triazoles (1a-f) and 1-benzoyl-3-phenyl-1,2,4-triazole (2) has been studied using kinetic methods. A comparison is drawn between medium effects in the micellar

  15. Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression

    Directory of Open Access Journals (Sweden)

    Takahiro Ebata

    2017-01-01

    Full Text Available The physical properties of the extracellular matrix (ECM, such as stiffness, are involved in the determination of the characteristics of cancer cells, including chemotherapy sensitivity. Resistance to chemotherapy is often linked to dysfunction of tumor suppressor p53; however, it remains elusive whether the ECM microenvironment interferes with p53 activation in cancer cells. Here, we show that, in MCF-7 breast cancer cells, extracellular stiffness influences p53 activation induced by the antitumor drug doxorubicin. Cell growth inhibition by doxorubicin was increased in response to ECM rigidity in a p53-dependent manner. The expression of Rho-associated coiled coil-containing protein kinase (ROCK 2, which induces the activation of myosin II, was significantly higher when cells were cultured on stiffer ECM substrates. Knockdown of ROCK2 expression or pharmacological inhibition of ROCK decreased doxorubicin-induced p53 activation. Our results suggest that a soft ECM causes downregulation of ROCK2 expression, which drives resistance to chemotherapy by repressing p53 activation.

  16. Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers.

    Directory of Open Access Journals (Sweden)

    Stefanie Wohlfart

    Full Text Available BACKGROUND: Chemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB prevents entry of most anticancer agents into the brain. For an efficient treatment of glioblastomas it is necessary to deliver anti-cancer drugs across the intact BBB. Poly(lactic-co-glycolic acid (PLGA nanoparticles coated with poloxamer 188 hold great promise as drug carriers for brain delivery after their intravenous injection. In the present study the anti-tumour efficacy of the surfactant-coated doxorubicin-loaded PLGA nanoparticles against rat glioblastoma 101/8 was investigated using histological and immunohistochemical methods. METHODOLOGY: The particles were prepared by a high-pressure solvent evaporation technique using 1% polyvinylalcohol (PLGA/PVA or human serum albumin (PLGA/HSA as stabilizers. Additionally, lecithin-containing PLGA/HSA particles (Dox-Lecithin-PLGA/HSA were prepared. For evaluation of the antitumour efficacy the glioblastoma-bearing rats were treated intravenously with the doxorubicin-loaded nanoparticles coated with poloxamer 188 using the following treatment regimen: 3 × 2.5 mg/kg on day 2, 5 and 8 after tumour implantation; doxorubicin and poloxamer 188 solutions were used as controls. On day 18, the rats were sacrificed and the antitumour effect was determined by measurement of tumour size, necrotic areas, proliferation index, and expression of GFAP and VEGF as well as Isolectin B4, a marker for the vessel density. CONCLUSION: The results reveal a considerable anti-tumour effect of the doxorubicin-loaded nanoparticles. The overall best results were observed for Dox-Lecithin-PLGA/HSA. These data demonstrate that the poloxamer 188-coated PLGA nanoparticles enable delivery of doxorubicin across the blood-brain barrier in the therapeutically effective concentrations.

  17. Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells.

    Science.gov (United States)

    Dash, Tapan K; Konkimalla, V Badireenath

    2017-02-01

    Curcumin is very well established as a chemo-therapeutic, chemo-preventive and chemo-sensitizing agent in diverse disease conditions. As the isolated pure form has poor solubility and pharmacokinetic problems, therefore it is encapsulated in to several nano-formulations to improve its bioavailability. Here in the current study, we aim to compare different nano-formulations of curcumin for their chemo-sensitizing activity in doxorubicin (DOX) resistant K562 cells. Four different curcumin formulations were prepared namely DMSO assisted curcumin nano-dispersion (CurD, 260 nm), liposomal curcumin (CurL, 165 nm), MPEG-PCL micellar curcumin (CurM, 18 nm) and cyclodextrin encapsulated curcumin (CurN, 37 nm). The formulations were subjected to particle characterizations (size, zeta potential, release studies), followed by biological assays such as cellular uptake, P-gp inhibitory activity and reversal of DOX resistance by co-treatment with DOX. Curcumin uptake in K562N and K562R cells was mildly reduced when treated with CurL and CurM, while for CurD and CurN the uptake remained equivalent. However, CurL retained P-gp inhibitory activity of curcumin and with a considerable chemo-sensitizing effect but CurM showed no P-gp inhibitory activity. CurN retained above biological activities, but requires a secondary carrier under in vivo conditions. From the results, CurM was found to be most suitable for solubilization of curcumin where as CurL can be considered as most suitable nano-formulation for reversal of DOX resistance.

  18. Effect of doxorubicin on cell survival and micronuclei formation in HeLa cells exposed to different doses of gamma-radiation

    International Nuclear Information System (INIS)

    Jagetia, G.C.; Nayak, V.

    2000-01-01

    Purpose: The present study was undertaken to obtain an insight into the combined effects of doxorubicin with radiation on the cell survival and micronuclei induction in HeLa cells. Material and Methods: HeLa S3 cells were allowed to grow till they reached plateau phase, inoculated with 10 μg/ml doxorubicin hydrochloride and then exposed to 0, 0.5, 1, 2 and 3 Gy γ-radiation. Clonogenicity of cell was measured using the colony forming assay, micronuclei formation using the micronucleus assay. Results: The treatment of HeLa cells with doxorubicin (adriamycin) for 2 hours before exposure to different doses of γ-radiation resulted in a significant and dose-dependent decline in the cell survival and cell proliferation when compared to the PBS+irradiation group. Conversely, the frequency of micronuclei increased in a dose-related manner in both the PBS+irradiation and doxorubicin+irradiation groups. The pretreatment of HeLa cells with doxorubicin before irradiation to various doses of γ-rays resulted in a significant elevation in the frequency of micronuclei when compared with the concurrent PBS+irradiation group. The dose-response relationship for both PBS+irradiation and doxorubicin+irradiation groups was linear. The correlation between cell survival and micronuclei induction was also determined for PBS or doxorubicin+irradiation group, where the clonogenicity of cells declined with the increase in micronuclei formation. The correlation between cell survical and micronuclei induction was linear quadratic for both PBS+irradiation and doxorubicin+irradiation groups. Conclusion: From our study it can be concluded that combination treatment with doxorubicin and radiation increased the genotoxic effect of the either treatment given alone. (orig.) [de

  19. Selective Killing of Breast Cancer Cells by Doxorubicin-Loaded Fluorescent Gold Nanoclusters: Confocal Microscopy and FRET.

    Science.gov (United States)

    Chattoraj, Shyamtanu; Amin, Asif; Jana, Batakrishna; Mohapatra, Saswat; Ghosh, Surajit; Bhattacharyya, Kankan

    2016-01-18

    Fluorescent gold nanoclusters (AuNCs) capped with lysozymes are used to deliver the anticancer drug doxorubicin to cancer and noncancer cells. Doxorubicin-loaded AuNCs cause the highly selective and efficient killing (90 %) of breast cancer cells (MCF7) (IC50 =155 nm). In contrast, the killing of the noncancer breast cells (MCF10A) by doxorubicin-loaded AuNCs is only 40 % (IC50 =4500 nm). By using a confocal microscope, the fluorescence spectrum and decay of the AuNCs were recorded inside the cell. The fluorescence maxima (at ≈490-515 nm) and lifetime (≈2 ns), of the AuNCs inside the cells correspond to Au10-13 . The intracellular release of doxorubicin from AuNCs is monitored by Förster resonance energy transfer (FRET) imaging. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. A theory of phase separation in asphaltene-micellar solutions

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco Sanchez, Juan H. [Instituto Mexicano del Petroleo, Mexico D.F. (Mexico)

    2001-08-01

    A theory of phase separation in micellar solutions of asphaltene in aromatic hydrocarbons was reported in this paper, based on both the approach of the phase behavior of amphiphile/water micelles, and the self-association of asphaltene in aromatic core. Several experimental techniques have been used by different investigators showing the existence of some kind of critical micellar concentration (CMC) on asphaltenes in aromatic solutions. So, at least asphaltene-monomer and asphaltene-micellar phases are experimentally demonstrated facts. These two phases are the main purpose in this report on a theoretical model. Some results show the temperature versus asphaltene concentration phase diagram. The phase diagram is examined against the limited critical micelle concentration data for asphaltenes-in-toluene systems. Such phase diagram is also qualitatively examined against an experimental demonstration of phase separation. The asphaltene-micelle growth depends on the parameter K responsible for the shape and size of it. At the same time, parameter K depends on both the number of asphaltene-monomer associated in the asphaltene-micelle, and the chemical potentials in the interior and in the periphery of the micelle. An expression for getting the number of asphaltene-monomers self-associated in the asphaltene-micelle was obtained. [Spanish] Se reporta una teoria de separacion de fases en soluciones micelares de asfalteno en hidrocarburos aromaticos, basada tanto en la conducta de fase de micelas formadas por anififilos en agua como en la autoasociacion de asfaltenos en nucleos aromaticos. Se han usado diversas tecnicas experimentales por diferentes investigadores que demuestran la existancia de algun tipo de concentracion micelar critica (CMC) de soluciones de asfaltenos en aromaticos. Entonces, al menos las fases de asfalteno-monomerico y de asfalteno-micelar son hechos experimentalmente demostrados. Esta dos fases son el principal proposito de este reporte en un modelo

  1. Eleutheroside E inhibits doxorubicin-induced inflammation and ...

    African Journals Online (AJOL)

    Purpose: To identify the effects of eleutheroside E (EE) on apoptosis and inflammation induced by doxorubicin (DOX) in H9c2 cells and to investigate the underlying mechanisms. Methods: The effect of EE on H9c2 cell viability was determined using Cell Counting Kit-8 (CCK8). EE effect on DOX-induced apoptosis and ...

  2. Infusion MR arteriography during hepatic arterial infusion chemotherapy. Evaluation of clinical usefulness

    International Nuclear Information System (INIS)

    Uchino, Minako; Takizawa, Kenji

    2003-01-01

    We developed a new method of infusion MR arteriography (IMRA) via an implantable port system using an infusion pump for the evaluation of drug distribution during hepatic arterial infusion chemotherapy. The purposes of this study were to optimize the method and evaluate its clinical usefulness. We used 3D-T1 turbo field echo (TFE) as the most suitable sequence for IMRA according to the results of a phantom model experiment. We examined 33 cases of liver cancer that had been treated by arterial infusion chemotherapy via the port system. The following investigations were performed: degree of tumor enhancement, intra- and extra- hepatic perfusion abnormality, and related toxicity. The evaluation of images was performed separately by two radiologists. IMRA provided good images of contrast enhancement, to reveal the perfusion patterns. The treatment response rate in the tumor group with well enhancement was higher than that of the group with poor enhancement (p<0.0001). Extrahepatic perfusion was well visualized and was correlated with toxicity (p<0.0001). IMRA is a useful method to evaluate drug perfusion for the optimization of arterial infusion chemotherapy. (author)

  3. Application of Surfactant Micellar Solutions as Extractants and Mobile Phases for TLC-Determination of Purine Bases and Doping Agents in Biological Liquids

    Directory of Open Access Journals (Sweden)

    Daria Victorovna Yedamenko

    2015-04-01

    Full Text Available Separation of caffeine and its metabolites (theophylline and theobromine and doping agents (spironolactone, propranolol, and ephedrine and determination of caffeine in serum sample and propranolol and ephedrine in urine were studied on normal-phase thin layers (“Sorbfil-UV-254”. Aqueous organic solvents and aqueous micellar surfactant solutions were compared as the mobile phases for separation. The acceptable separation of purine bases and doping agents was achieved by micellar Thin Layer Chromatography and normal-phase Thin Layer Chromatography. Anionic surfactant solution with added 1-propanol was the best eluent as for caffeine, theophylline, and theobromine separation, as for doping agents. The best characteristics of caffeine extraction from serum, and propranolol and ephedrine from urine were achieved when micellar eluent based on non-ionic Tween-80 surfactant was used. DOI: http://dx.doi.org/10.17807/orbital.v7i1.632

  4. Age-related effect of aerobic exercise training on antioxidant and oxidative markers in the liver challenged by doxorubicin in rats.

    Science.gov (United States)

    Ahmadian, Mehdi; Dabidi Roshan, Valiollah; Leicht, Anthony S

    2018-05-16

    The aims of the current study were to investigate the oxidant and antioxidant status of liver tissue challenged by doxorubicin and to examine the possible protective effects of aerobic exercise on doxorubicin-induced oxidative stress. Seventy-two rats were divided into three age groups (Young, Adult, and Elderly) with three treatment subgroups consisting of eight rats per age group: doxorubicin, aerobic exercise + doxorubicin, and aerobic exercise + saline. The experimental groups performed regular treadmill running for 3 weeks. Doxorubicin was administered by i.p. injection at a dosage of 20 mg kg -1 while the aerobic exercise + saline group received saline of a comparable volume. Heat shock protein 70, malondialdehyde, glutathione peroxidase, and protein carbonyl were determined from the liver homogenates following the intervention period. Treatment with doxorubicin induced hepatotoxicity in all groups with lower values of oxidative stress in young compared with the older groups. The inclusion of aerobic exercise training significantly increased heat shock protein 70 and antioxidant enzyme levels (glutathione peroxidase) whereas it decreased oxidative stress biomarkers (malondialdehyde and protein carbonyl) for all age groups. These results suggest that aerobic exercise training may be a potential, non-drug strategy to modulate doxorubicin-induced hepatotoxicity through its positive impact on antioxidant levels and oxidative stress biomarkers.

  5. An audit of hospital based outpatient infusions and a pilot program of community-based monoclonal antibody infusions.

    LENUS (Irish Health Repository)

    Doran, J-P

    2012-02-01

    INTRODUCTION: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor alpha, is administered as an intravenous infusion requiring a costly hospital day case or inpatient admission. METHODS: An audit of all current therapies given by intravenous infusions in an outpatient setting in St Vincent\\'s University Hospital (SVUH) was undertaken. Furthermore, in conjunction with TCP homecare, we established in a general practise health clinic, the first Irish community infusion centre for the administration of infliximab in August 2006. RESULTS: All outpatient departments indicated that they would favour a centralized hospital infusion unit. There were no adverse events and the mean global satisfaction improved in the community infliximab infusion pilot programme of seven patients. CONCLUSION: This study suggests efficiencies in providing centralized infusion facilities, while the community based infusion of infliximab is feasible and safe in this small cohort and identifies the community infusion unit as a viable and cost efficient alternative for administration of infliximab.

  6. Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGFβ.

    Directory of Open Access Journals (Sweden)

    Tapasi Rana

    Full Text Available Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002 and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005, both of which were rescued by anti-TGFβ antibody (1D11. Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC. Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1 expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients.

  7. Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma.

    Science.gov (United States)

    Marley, Kevin; Helfand, Stuart C; Simpson, Jennifer; Mata, John E; Tracewell, William G; Brownlee, Lisa; Bracha, Shay; Séguin, Bernard

    2013-10-11

    Osteosarcoma in dogs and humans share many similarities and the dog has been described as an excellent model to study this disease. The median survival in dogs has not improved in the last 25 years. Taurolidine has been shown to be cytotoxic to canine and human osteosarcoma in vitro. The goals of this study were to determine the pharmacokinetics and safety of taurolidine in healthy dogs and the safety of taurolidine in combination with doxorubicin or carboplatin in dogs with osteosarcoma. Two percent taurolidine was infused into six healthy dogs (150 mg/kg) over a period of two hours and blood samples were taken periodically. One dog received taurolidine with polyvinylpyrrolidone (PVP) as its carrier and later received PVP-free taurolidine as did all other dogs in this study. Serum taurolidine concentrations were determined using high-performance liquid chromatography (HPLC) online coupled to ESI-MS/MS in the multiple reaction monitoring mode. Subsequently, the same dose of taurolidine was infused to seven dogs with osteosarcoma also treated with doxorubicin or carboplatin. Taurolidine infusion was safe in 6 healthy dogs and there were no significant side effects. Maximum taurolidine serum concentrations ranged between 229 to 646 μM. The dog that received taurolidine with PVP had an immediate allergic reaction but recovered fully after the infusion was stopped. Three additional dogs with osteosarcoma received doxorubicin and taurolidine without PVP. Toxicities included dilated cardiomyopathy, protein-losing nephropathy, renal insufficiency and vasculopathy at the injection site. One dog was switched to carboplatin instead of doxorubicin and an additional 4 dogs with osteosarcoma received taurolidine-carboplatin combination. One incidence of ototoxicity occurred with the taurolidine- carboplatin combination. Bone marrow and gastro-intestinal toxicity did not appear increased with taurolidine over doxorubicin or carboplatin alone. Taurolidine did not

  8. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

    Science.gov (United States)

    Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

    2017-08-01

    Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

  9. Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model.

    Science.gov (United States)

    Chugh, R; Griffith, K A; Davis, E J; Thomas, D G; Zavala, J D; Metko, G; Brockstein, B; Undevia, S D; Stadler, W M; Schuetze, S M

    2015-07-01

    Insulin-like growth factor receptor (IGF-1R) has been studied as an oncologic target in soft tissue sarcoma (STS), but its role in sarcoma biology is unclear. Anti-IGF-1R antibody cixutumumab demonstrated acceptable toxicity but limited activity as a single agent in STS. We carried out a dose-escalation study of cixutumumab with doxorubicin to evaluate safety and dosing of the combination. Eligible patients with advanced STS were treated with cixutumumab intravenously on days 1/8/15 at one of three dose levels (A: 1 mg/kg, B: 3 mg/kg, C: 6 mg/kg) with doxorubicin at 75 mg/m(2) as a 48 h infusion on day 1 of a 21 day cycle. After six cycles of the combination, patients could receive cixutumumab alone. The Time-to-Event Continual Reassessment Method was used to estimate the probability of dose-limiting toxicity (DLT) and to assign patients to the dose with an estimated probability of DLT≤20%. Between September 2008 and January 2012, 30 patients with advanced STS received a median of six cycles of therapy (range <1-22). Two DLTs were observed, grade 3 mucositis (dose level B) and grade 4 hyperglycemia (dose level C). Grade 2 and 3 reduced left ventricular ejection fraction was seen in three and two patients, respectively. Five partial responses were observed, and estimated progression-free survival was 5.3 months (95% confidence interval 3.0-6.3) in 26 response-assessable patients. Immunohistochemical staining of 11 available tumor samples for IGF-1R and phospho-IGF-1R was not significantly different among responders and non-responders, and serum analysis of select single-nucleotide polymorphisms did not predict for cardiotoxicity. The maximum tolerated dose was doxorubicin 75 mg/m(2) on day 1 and cixitumumab 6 mg/kg on days 1/8/15 of a 21 day cycle. Cardiac toxicity was observed and should be monitored in subsequent studies, which should be considered in STS only if a predictive biomarker of benefit to anti-IGF-1R therapy is identified. Clinical

  10. Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab

    Directory of Open Access Journals (Sweden)

    Yousefpour P

    2011-09-01

    Full Text Available Parisa Yousefpour1, Fatemeh Atyabi2, Ebrahim Vasheghani-Farahani3, Ali-Akbar Mousavi Movahedi1, Rassoul Dinarvand21Department of Biotechnology, Faculty of Science, University of Tehran, 2Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, 3Biotechnology Group, Department of Chemical Engineering, Faculty of Engineering, Tarbiat Modares University, Tehran, IranBackground: Targeting drugs to their sites of action to overcome the systemic side effects associated with most antineoplastic agents is still a major challenge in pharmaceutical research. In this study, the monoclonal antibody, trastuzumab, was used as a targeting agent in nanoparticles carrying the antitumor drug, doxorubicin, specifically to its site of action.Methods: Chitosan-doxorubicin conjugation was carried out using succinic anhydride as a crosslinker. Trastuzumab was conjugated to self-assembled chitosan-doxorubin conjugate (CS-DOX nanoparticles (particle size, 200 nm via thiolation of lysine residues and subsequent linking of the resulted thiols to chitosan. Conjugation was confirmed by gel permeation chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy studies. Dynamic light scattering, transmission electron microscopy, and zeta potential determination were used to characterize the nanoparticles.Results: CS-DOX conjugated nanoparticles had a spherical shape and smooth surface with a narrow size distribution and core-shell structure. Increasing the ratio of doxorubicin to chitosan in the conjugation reaction gave rise to a higher doxorubicin content but lower conjugation efficiency. Trastuzumab-decorated nanoparticles (CS-DOX-mAb contained 47 µg/mg doxorubicin and 33.5 µg/mg trastuzumab. Binding of trastuzumab to the nanoparticles was further probed thermodynamically by isothermal titration calorimetry. Fluorescence microscopy demonstrated enhanced and

  11. Bronchial arterial infusion versus bronchial combined pulmonary arterial infusion for pulmonary metastatic tumors

    International Nuclear Information System (INIS)

    Dong Sheng; Dong Weihua; Jia Ningyang; Zhang Dianbo; Xiao Xiangsheng

    2008-01-01

    Objective: To evaluate the pulmonary metastatic tumor response to different ways of transcatheter arterial infusion. Methods: Thirty-five patients with pulmonary metastatic tumors were randomized divided into two groups: 15 patients with 49 lesions treated with bronchial arterial infusion (BAI) and 20 patients with 65 lesions treated with bronchial arterial infusion (BM)combined with pulmonary arterial infusion (PAI). The therapeutic response was assessed by the WHO evaluation criteria. Results: The total effective rate(CR + PR) of BAI was 65.3% (32/49), PAI + BAI was 61.5%(40/65) showing no statistical difference. The median survival time of BAI was 9 mo, BAI + PAI was 11.5 mo, demonstrating no statistical significance. Conclusions: BAI should be the primary treatment for pulmonary metastatic tumor. (authors)

  12. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

    Directory of Open Access Journals (Sweden)

    Leonhard V

    2015-05-01

    Full Text Available Victoria Leonhard,1,2 Roxana V Alasino,1,2 Ismael D Bianco,1–3 Ariel G Garro,1 Valeria Heredia,1 Dante M Beltramo1,2,4 1Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR, Córdoba, Argentina; 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Buenos Aires, Argentina; 3Departamento de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de La Rioja, La Rioja, Argentina; 4Laboratorio de Biotecnología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina Abstract: Doxorubicin (Dox is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1 ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx. However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C. Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the

  13. Mesenchymal Stem Cells Reduce Left Ventricular Mass in Rats with Doxorubicin-Induced Cardiomyopathy

    OpenAIRE

    Haydardedeoglu, Ali Evren; Boztok Özgermen, Deva Basak; Yavuz, Orhan

    2018-01-01

    SUMMARY: Doxorubicin is a drug that used by a majority in the treatment of carcinomas. The most obvious known side effect is cardiomyopathy. Many studies have been carried out to eliminate side effects of the doxorubicin, and stem cell studies have been added in recent years. In this study, it was aimed to investigate fetal-derived mesenchymal stem cells (F-MSCs) treatment of doxorubicininduced cardiomyopathy by morphological methods. A total of 24 rats which were divided into three separate ...

  14. Mechanism of protection of moderately diet restricted rats against doxorubicin-induced acute cardiotoxicity

    International Nuclear Information System (INIS)

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Latendresse, John R.; Mehendale, Harihara M.

    2007-01-01

    Clinical use of doxorubicin (Adriamycin (registered) ), an antitumor agent, is limited by its oxyradical-mediated cardiotoxicity. We tested the hypothesis that moderate diet restriction protects against doxorubicin-induced cardiotoxicity by decreasing oxidative stress and inducing cardioprotective mechanisms. Male Sprague-Dawley rats (250-275 g) were maintained on diet restriction [35% less food than ad libitum]. Cardiotoxicity was estimated by measuring biomarkers of cardiotoxicity, cardiac function, lipid peroxidation, and histopathology. A LD 100 dose of doxorubicin (12 mg/kg, ip) administered on day 43 led to 100% mortality in ad libitum rats between 7 and 13 days due to higher cardiotoxicity and cardiac dysfunction, whereas all the diet restricted rats exhibited normal cardiac function and survived. Toxicokinetic analysis revealed equal accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the ad libitum and diet restricted hearts. Mechanistic studies revealed that diet restricted rats were protected due to (1) lower oxyradical stress from increased cardiac antioxidants leading to downregulation of uncoupling proteins 2 and 3, (2) induction of cardiac peroxisome proliferators activated receptor-α and plasma adiponectin increased cardiac fatty acid oxidation (666.9 ±14.0 nmol/min/g heart in ad libitum versus 1035.6 ± 32.3 nmol/min/g heart in diet restriction) and mitochondrial AMPα2 protein kinase. The changes led to 51% higher cardiac ATP levels (17.7 ± 2.1 μmol/g heart in ad libitum versus 26.7 ± 1.9 μmol/g heart in diet restriction), higher ATP/ADP ratio, and (3) increased cardiac erythropoietin and decreased suppressor of cytokine signaling 3, which upregulates cardioprotective JAK/STAT3 pathway. These findings collectively show that moderate diet restriction renders resiliency against doxorubicin cardiotoxicity by lowering oxidative stress, enhancing ATP synthesis, and inducing the JAK/STAT3 pathway

  15. Hydrophobically modified inulin as an amphiphilic carbohydrate polymer for micellar delivery of paclitaxel for intravenous route.

    Science.gov (United States)

    Muley, Pratik; Kumar, Sunny; El Kourati, Fadoua; Kesharwani, Siddharth S; Tummala, Hemachand

    2016-03-16

    Micellization offers several advantages for the delivery of water insoluble drugs including a nanoparticulate 'core-shell' delivery system for drug targeting. Recently, hydrophobically modified polysaccharides (HMPs) are gaining recognition as micelle forming polymers to encapsulate hydrophobic drugs. In this manuscript, for the first time, we have evaluated the self-assembling properties of a lauryl carbamate derivative of the poly-fructose natural polymer inulin (Inutec SP1(®) (INT)) to form paclitaxel (PTX) loaded micelles. INT self-assembled into well-defined micellar structures in aqueous environment with a low critical micellar concentration of 27.8 μg/ml. INT micelles exhibited excellent hemocompatibility and low toxicity to cultured cells. PTX loaded INT micelles exhibited a mean size of 256.37 ± 10.45 nm with excellent drug encapsulation efficiency (95.66 ± 2.25%) and loading (8.69 ± 0.22%). PTX loaded micelles also displayed sustained release of PTX and enhanced anti-cancer efficacy in-vitro in mouse melanoma cells (B16F10) compared to Taxol formulation with Cremophor EL as solvent. In addition, PTX loaded INT micelles exhibited comparable in-vivo antitumor activity in B16F10 allograft mouse model at half the dose of Taxol. In conclusion, INT offers safe, inexpensive and natural alternative to widely used PEG-modified polymers for the formulation of micellar delivery systems for paclitaxel. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    International Nuclear Information System (INIS)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-01-01

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn 2+ and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase + was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights:

  17. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui, E-mail: Donghuixu007@163.com

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn{sup 2+} and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase{sup +} was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights:

  18. Hesperidin as a preventive resistance agent in MCF–7 breast cancer cells line resistance to doxorubicin

    Directory of Open Access Journals (Sweden)

    Rifki Febriansah

    2014-03-01

    Conclusions: Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC50 of 11 μmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.

  19. Deracemization of bilirubin as the marker of the chirality of micellar aggregates.

    Science.gov (United States)

    Sorrenti, Alessandro; Altieri, Barbara; Ceccacci, Francesca; Di Profio, Pietro; Germani, Raimondo; Giansanti, Luisa; Savelli, Gianfranco; Mancini, Giovanna

    2012-01-01

    The deracemization of bilirubin in micellar aggregates of structurally correlated chiral surfactants was studied by circular dichroism experiments and exploited as the marker of the expression of chirality of the aggregates. The obtained results suggest that the hydrophobic interactions control the transfer of chirality from the monomers to the aggregates, and that different regions of the same aggregate might feature opposite enantiorecognition capabilities. Copyright © 2011 Wiley-Liss, Inc.

  20. Effect of steel and teflon infusion catheters on subcutaneous adipose tissue blood flow and infusion counter pressure in humans

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Skov-Jensen, Camilla; Kaastrup, Peter

    2009-01-01

    BACKGROUND: Subcutaneous tissue is an important target for drug deposition or infusion. A local trauma may induce alterations in local microcirculation and diffusion barriers with consequences for drug bioavailability. We examined the influence of infusion catheters' wear time on local...... microcirculation and infusion counter pressure. METHODS: One steel catheter and one Teflon (Dupont, Wilmington, DE) catheter were inserted in subcutaneous, abdominal adipose tissue (SCAAT) in 10 healthy, lean men. The catheters were infused with isotonic saline at a rate of 10 microL/h for 48 h. Another steel...... catheter and a Teflon catheter were inserted contralateral to the previous catheters after 48 h. The infusion counter pressure was measured during a basal infusion rate followed by a bolus infusion. The measurements during a basal rate infusion were repeated after the bolus infusion. Adipose tissue blood...

  1. Studies on the effect of doxorubicin on MDA, NO2, NO3, Se-GSH ...

    African Journals Online (AJOL)

    SERVER

    2007-10-18

    Oct 18, 2007 ... Nitric oxide; NO2. - Nitric oxide; NO3- ... The lipid peroxides were determined by the TBA me- ... Effect of different doses of doxorubicin on rat serum nitrite (NO2 .... 2306. Afr. J. Biotechnol. 0. 5. 10. 15. 20. 25. 30. P e rc e n. t c h a n g e o v e ... Doxorubicin induced percent changes of rat serum Nitrate (NO3.

  2. Comparison of Docetaxel, Doxorubicin and Cyclophosphamide (TAC with 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Phase III Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadianpanah

    2011-04-01

    Full Text Available Background: The present study aimed to compare the rates of complete clinical and pathologic response to docetaxel, doxorubicin and cyclophosphamide (TAC vs. 5-fluorouracil, doxorubicin and cyclophosphamide (FAC as neoadjuvant chemotherapy in women with locally advanced breast cancer.Methods: One hundred women with pathologically confirmed newly diagnosed locally advanced (T3-T4 or N2-N3 breast cancer were randomly assigned to receive a median of four cycles of either 5-fluorouracil (600 mg/m2, doxorubicin (60 mg/m2 and cyclophosphamide (600 mg/m2 every three weeks or docetaxel (75 mg/m2, doxorubicin (50 mg/m2 and cyclophosphamide (500 mg/m2 every three weeks followed by modified radical mastectomy. Complete clinical and pathologic response rates and toxicity were the primary and secondary outcome measures of the study. Results: Median age for all patients was 43.4 years (range 25-63 years. Patients in the TAC arm achieved a higher clinical (16% response rate than those in the FAC arm (4%, P=0.046. The pathologic response rate was also higher in the TAC arm compared to the FAC arm [TAC (20% vs. FAC (6%, P=0.037]. Estrogen receptor-negative status correlated with a higher clinical [TAC (19% vs. FAC (4%, P=0.032]and pathologic [TAC (23% vs. FAC (4%, P=0.011] response rate in both arms. All patients generally tolerated treatment well, and treatment-related toxicities were manageable. Conclusion: Combined treatment with TAC led to higher rates of complete clinical and pathologic response with acceptable toxicity compared to FAC in patients with locally advanced breast cancer. However, further follow-up is needed to translate this response into improvements in survival.

  3. Clinical Trials with Pegylated Liposomal Doxorubicin in the Treatment of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Carmela Pisano

    2013-01-01

    Full Text Available Among the pharmaceutical options available for treatment of ovarian cancer, increasing attention has been progressively focused on pegylated liposomal doxorubicin (PLD, whose unique formulation prolongs the persistence of the drug in the circulation and potentiates intratumor accumulation. Pegylated liposomal doxorubicin (PLD has become a major component in the routine management of epithelial ovarian cancer. In 1999 it was first approved for platinum-refractory ovarian cancer and then received full approval for platinum-sensitive recurrent disease in 2005. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Recent interest in PLD/carboplatin combination therapy has been the object of phase III trials in platinum-sensitive and chemonaïve ovarian cancer patients reporting response rates, progressive-free survival, and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule. This paper summarizes data clarifying the role of pegylated liposomal doxorubicin (PLD in ovarian cancer, as well as researches focusing on adding novel targeted drugs to this cytotoxic agent.

  4. Preparation, quality control and biodistribution of [61Cu]-doxorubicin for PET imaging

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Akhlaghi, M.; Zandi, H.; Yousefnia, H.; Faghihi, R.

    2009-01-01

    This work was conducted for radiolabeling of an anticancer antibiotic, i.e. doxorubicin with 61 Cu for production of possible tracer used in PET oncology. 61 Cu was prepared with natural zinc target and 22 MeV 150 μA protons via nat Zn(p, xn) 61 Cu reaction with a yield of 123.2 MBq·μA -1 ·h -1 . Optimization reactions were performed for pH, temperature and concentration. Biodistribution of the tracer was studied in normal and fibrosarcoma bearing mice. At the optimized conditions, ITLC showed that radiochemical purity was over 97% with a specific activity of 2.22 X 10 3 MBq·mmol -1 ·L -1 . This was kept unchanged even with presence of human serum as well as room temperature for 5 h. Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated significant tumor uptake after 2 h. This tracer can be used in the detection of various tumors responding to doxorubicin chemotherapy using PET scan and/or determination of tumor therapy response to doxorubicin chemotherapy. (authors)

  5. A Phase I Study of Triapine® in Combination with Doxorubicin in Patients with Advanced Solid Tumors

    Science.gov (United States)

    Schelman, William R.; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M.; Ivy, Percy; Wilding, George; Traynor, Anne M.

    2011-01-01

    Purpose To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine® administered in combination with doxorubicin. Study Design Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine® IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m2 and Triapine® 25 mg/m2. PK analysis was performed at various time-points before and after treatment. Results Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m2, Triapine® 45 mg/m2), 2 patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional 3 patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m2) with Triapine® 45 mg/m2. The 2 patients enrolled on this level had 2 DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine® were reduced to 45 mg/m2 and 25 mg/m2, respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Conclusions Pretreated patients with advanced malignancies can tolerate the combination of Triapine® and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m2 on day 1 and Triapine® 25 mg/m2 on

  6. Potentiation of apoptosis by histone deacetylase inhibitors and doxorubicin combination: cytoplasmic cathepsin B as a mediator of apoptosis in multiple myeloma.

    Science.gov (United States)

    Cheriyath, V; Kuhns, M A; Kalaycio, M E; Borden, E C

    2011-03-15

    Although inhibitors of histone deacetylase inhibitors (HDACis) in combination with genotoxins potentiate apoptosis, the role of proteases other than caspases in this process remained elusive. Therefore, we examined the potentiation of apoptosis and related mechanisms of HDACis and doxorubicin combination in a panel of myeloma cell lines and in 25 primary myelomas. At IC(50) concentrations, sodium butyrate (an HDACi) or doxorubicin alone caused little apoptosis. However, their combination potentiated apoptosis and synergistically reduced the viability of myeloma cells independent of p53 and caspase 3-7 activation. Potentiated apoptosis correlated with nuclear translocation of apoptosis-inducing factor, suggesting the induction of caspase 3- and 7-independent pathways. Consistent with this, butyrate and doxorubicin combination significantly increased the activity of cytoplasmic cathepsin B. Inhibition of cathepsin B either with a small-molecule inhibitor or downregulation with a siRNA reversed butyrate- and doxorubicin-potentiated apoptosis. Finally, ex vivo, clinically relevant concentrations of butyrate or SAHA (suberoylanilide hydroxamic acid, vorinostat, an HDACi in clinical testing) in combination with doxorubicin significantly (Pmediating apoptosis potentiated by HDACi and doxorubicin combinations in myeloma. Our results support a molecular model of lysosomal-mitochondrial crosstalk in HDACi- and doxorubicin-potentiated apoptosis through the activation of cathepsin B.

  7. Hippocampal infusions of glucose reverse memory deficits produced by co-infusions of a GABA receptor agonist.

    Science.gov (United States)

    Krebs-Kraft, Desiree L; Parent, Marise B

    2008-02-01

    Although septal infusions of glucose typically have positive effects on memory, we have shown repeatedly that this treatment exacerbates memory deficits produced by co-infusions of gamma-aminobutyric acid (GABA) receptor agonists. The present experiments tested whether this negative interaction between glucose and GABA in the medial septum would be observed in the hippocampus, a brain region where glucose typically has positive effects on memory. Specifically, we determined whether hippocampal infusions of glucose would reverse or exacerbate memory deficits produced by hippocampal co-infusions of the GABA receptor agonist muscimol. Fifteen minutes prior to either assessing spontaneous alternation (SA) or continuous multiple trial inhibitory avoidance (CMIA) training, male Sprague-Dawley-derived rats were given bilateral hippocampal infusions of vehicle (phosphate-buffered saline [PBS], 1 microl/2 min), glucose (33 or 50 nmol), muscimol (0.3 or 0.4 microg, SA or 3 microg, CMIA) or muscimol and glucose combined in one solution. The results indicated that hippocampal infusions of muscimol alone decreased SA scores and CMIA retention latencies. More importantly, hippocampal infusions of glucose, at doses that had no effect when infused alone, attenuated (33 nmol) or reversed (50 nmol) the muscimol-induced memory deficits. Thus, although co-infusions of glucose with muscimol into the medial septum impair memory, the present findings show that an opposite effect is observed in the hippocampus. Collectively, these findings suggest that the memory-impairing interaction between glucose and GABA in the medial septum is not a general property of the brain, but rather is brain region-dependent.

  8. Mangifera indica L. leaf extract alleviates doxorubicin induced cardiac stress

    Directory of Open Access Journals (Sweden)

    Laxit Bhatt

    2017-09-01

    Conclusion: The present findings clearly suggest the protective role of alcoholic leaf extract of M. indica against oxidative stress induced by doxorubicin. [J Complement Med Res 2017; 6(3.000: 284-289

  9. Marginalism, quasi-marginalism and critical phenomena in micellar solutions

    International Nuclear Information System (INIS)

    Reatto, L.

    1986-01-01

    The observed nonuniversal critical behaviour of some micellar solutions is interpreted in terms of quasi-marginalism, i.e. the presence of a coupling which scales with an exponent very close to the spatial dimensionality. This can give rise to a preasymptotic region with varying effective critical exponents with a final crossover to the Ising ones. The reduced crossover temperature is estimated to be below 10 -6 . The exponents β and γ measured in C 12 e 5 are in good agreement with the scaling law expected to hold for the effective exponents. The model considered by Shnidman is found unable to explain the nonuniversal critical behaviour

  10. Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

    Science.gov (United States)

    Gabriel, Janice

    2014-11-01

    Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set.

  11. Serial exercise gated radionuclide ventriculograms (RVG) in monitoring doxorubicin cardiotoxicity

    International Nuclear Information System (INIS)

    Goldstein, H.A.; Lahoda, J.; Fox, L.

    1985-01-01

    The resting RVG (Radionuclide Ventriculograms) are demonstrated to be an effective monitor of the cardiotoxicity of doxorubicin. The exercise RVG has not been as well studied to see if it yields additional information or detects toxicity effects earlier. Sixteen patients receiving doxorubicin for chemotherapy had 2-6 serial exercise studies with intervals between studies of 1 month to 15 months. The patients exercised varying amounts with cardiac work indicated by their double products (HR x Sys. BP). Although all patients started with a normal resting LVEF (>50%), 5 of the 16 did not have a normal response (≥5% increase in LVEF) with initial exercise study. Of the 11 patients with an initially normal response to exercise, on at least one subsequent study, 3 had an abnormal response to exercise. On a later follow up study 1 of these 3 patients again had a normal response to exercise. Six of these 11 patients had had RVG evidence of cardiotoxicity. Four of these 6 patients had continually normal exercise responses, while 2 of these 5 patients had had an abnormal exercise response. An initial exercise RVG may be reasonable to detect unsuspected CAD in cancer victims. These patients are reported to be more sensitive to the toxic effects of doxorubicin. Follow up exercise RVGs do not contribute useful information, do not predict cardiotoxicity, and may be misleading

  12. C(60 fullerene prevents genotoxic effects of doxorubicin in human lymphocytes in vitro

    Directory of Open Access Journals (Sweden)

    K. S. Afanasieva

    2015-02-01

    Full Text Available The self-ordering of C60 fullerene, doxorubicin and their mixture precipitated from aqueous solutions was investigated using atomic-force microscopy. The results suggest the complexation between the two compounds. The genotoxicity of doxorubicin in complex with C60 fullerene (С60+Dox was evaluated in vitro with comet assay using human lymphocytes. The obtained results show that the C60 fullerene prevents the toxic effect of Dox in normal cells and, thus, С60+Dox complex might be proposed for biomedical application.

  13. Micellar and analytical implications of a new potentiometric PVC sensor based on neutral ion-pair complexes of dodecylmethylimidazolium bromide-sodium dodecylsulfate.

    Science.gov (United States)

    Sanan, Reshu; Mahajan, Rakesh Kumar

    2013-03-15

    With an aim to characterize the micellar aggregates of imidazolium based ionic liquids, a new potentiometric PVC sensor based on neutral ion-pair complexes of dodecylmethylimidazolium bromide-sodium dodecylsulfate (C12MeIm(+)DS(-)) has been developed. The electrode exhibited a linear response for the concentration range of 7.9×10(-5)-9.8×10(-3) M with a super-Nernstian slope of 92.94 mV/decade, a response time of 5 s and critical micellar concentration (cmc) of 10.09 mM for C12MeImBr. The performance of the electrode in investigating the cmc of C12MeImBr in the presence of two drugs [promazine hydrochloride (PMZ) and promethazine hydrochloride (PMT)] and three triblock copolymers (P123, L64 and F68) has been found to be satisfactory on comparison with conductivity measurements. Various micellar parameters have been evaluated for the binary mixtures of C12MeImBr with drugs and triblock copolymers using Clint's, Rubingh's, and Motomura's approach. Thus the electrode offers a simple, straightforward and relatively fast technique for the characterization of micellar aggregates of C12MeImBr, complementing existing conventional techniques. Further, the analytical importance of proposed C12MeIm(+)-ISE as end point indicator in potentiometric titrations and for direct determination of cationic surfactants [cetylpyridinium chloride (CPC), tetradecyltrimethylammonium bromide (TTAB), benzalkonium chloride (BC)] in some commercial products was judged by comparing statistically with classical two-phase titration methods. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Sildenafil citrate improves the delivery and anticancer activity of doxorubicin formulations in a mouse model of breast cancer.

    Science.gov (United States)

    Greish, Khaled; Fateel, Maryam; Abdelghany, Sara; Rachel, Nanitha; Alimoradi, Houman; Bakhiet, Moiz; Alsaie, Ahmed

    2017-11-21

    Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of sildenafil on tumour vasculatures could result in an improvement of anticancer drug concentration in tumour tissues and hence improves its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro. Adding 1, 30 and 100 μM of Viagra to 1 μM of doxorubicin resulted in 1.8-fold, 6.2-fold and 21-fold statistically significant increases in its cytotoxic effect, respectively. As a result, 4T1 tumour-bearing mice showed up to 2.7-fold increase in drug concentrations of the fluorescent Dye DiI and doxorubicin in tumour tissues, as well as their nanoformulations. Animals treated with the combinations of both Sildenafil citrate and doxorubicin showed a statistically significant 4.7-fold reduction in tumour size compared to doxorubicin alone. This work highlights the effect of Sildenafil on tumour vasculatures and provides a rational for further testing the combination on breast cancer patients.

  15. Jet A fuel recovery using micellar flooding: Design and implementation.

    Science.gov (United States)

    Kostarelos, Konstantinos; Lenschow, Søren R; Stylianou, Marinos A; de Blanc, Phillip C; Mygind, Mette Marie; Christensen, Anders G

    2016-09-01

    Surfactants offer two mechanisms for recovering NAPLs: 1) to mobilize NAPL by reducing NAPL/water interfacial tension, and; 2) to increase the NAPL's aqueous solubility-called solubilization-as an enhancement to pump & treat. The second approach has been well-studied and applied successfully in several pilot-scale and a few full-scale tests within the last 15years, known as Surfactant Enhanced Aquifer Remediation (SEAR). A useful source of information for this second approach is the "Surfactant-enhanced aquifer remediation (SEAR) design manual" from the U.S. Navy Facilities Engineering Command. Few attempts, however, have been made at recovering NAPLs using the mobilization approach presented in this paper. Now, a full-scale field implementation of the mobilization approach is planned to recover an LNAPL (Jet A fuel) from a surficial sand aquifer located in Denmark using a smaller amount of surfactant solution and fewer PVs of throughput compared with the SEAR approach. The approach will rely on mobilizing the LNAPL so that it is recovered ahead of the surfactant microemulsion, also known as a micellar flood. This paper will review the laboratory work performed as part of the design for a full-scale implementation of a micellar flood. Completed lab work includes screening of surfactants, phase behavior and detailed salinity scans of the most promising formulations, and generating a ternary diagram to be used for the numerical simulations of the field application. The site owners and regulators were able to make crucial decisions such as the anticipated field results based on this work. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Histopathological effects of doxorubicin on pancreas in male albino rats

    Directory of Open Access Journals (Sweden)

    I.A. Ali

    2015-06-01

    Full Text Available The aim of this study was to investigate the histopathological side effects of doxorubicin on pancreas tissue in male albino rats Rattus norvegicus. This study were used 55 adult rats (2.5-3.5 month of age. The rats divided into two groups, the first group include (35 rats. The second group were (20 rats. Microscopial examination of pancreas lesion demonstrated oedema around the acini, swelling of the epithelial cells of acini, occurance of cystic fibrosis (mucoviscidosis at the concentration of (4,5 mg/kg of body weight ,occurrence of small islets that form of few cells and exocrine-endocrine transformation. There were thickness in the walls of blood vessels, thrombus, congestion of blood vessels, we conclude, that doxorubicin had histopathological effect on pancreas in sub-acute doses more than chronic doses.

  17. Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing

    DEFF Research Database (Denmark)

    Jensen, Vivi Flou Hjorth; Molck, Anne-Marie; Martensson, Martin

    2017-01-01

    compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model...... which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous...... infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model....

  18. The effect of HCV serological status on Doxorubicin based ...

    African Journals Online (AJOL)

    Background: Breast cancer and HCV are two frequent diseases in Egypt. There is a considerable probability of concurrent affection. This concurrence creates a subpopulation, which needs special evaluation and care. Objective: To evaluate a subset of Egyptian breast cancer patients receiving Doxorubicin based adjuvant ...

  19. Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Lee SJ

    2015-08-01

    Full Text Available Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol (MPEG-doxorubicin (DOX conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP. Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP. Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and

  20. Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Lulu Fan

    Full Text Available BACKGROUND: Endoplasmic reticulum stress (ER stress is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone, is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress-induced resistance to chemotherapeutic agents in hepatocellular carcinoma (HCC are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the effect of the endoplasmic reticulum (ER stress response during resistance of human hepatocellular carcinoma cells to doxorubicin. Treatment with the ER stress-inducer tunicamycin (TM before the addition of doxorubicin reduced the rate of apoptosis induced by doxorubicin. Interestingly, co-pretreatment with tunicamycin and Pae significantly increased apoptosis induced by doxorubicin. Furthermore, induction of ER stress resulted in increasing expression of COX-2 concomitant with inactivation of Akt and up-regulation of the pro-apoptotic transcription factor CHOP (GADD153 in HepG2 cells. These cellular changes in gene expression and Akt activation may be an important resistance mechanism against doxorubicin in hepatocellular carcinoma cells undergoing ER stress. However, co-pretreatment with tunicamycin and Pae decreased the expression of COX-2 and levels of activation of Akt as well as increasing the levels of CHOP in HCC cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Pae reverses ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by targeting COX-2 mediated inactivation of PI3K/AKT/CHOP.

  1. Pharmacological stimulation of p53 with low-dose doxorubicin ameliorates diet-induced nonalcoholic steatosis and steatohepatitis

    Directory of Open Access Journals (Sweden)

    Begoña Porteiro

    2018-02-01

    Full Text Available Objective: Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH. Methods: We used long-term pharmacological activation of p53 by i.p. or oral administration of low-dose doxorubicin in different animal models of NAFLD (high fat diet containing 45% and 60% kcal fat and NASH (methionine- and choline-deficient diet and choline deficiency combined with high fat diet. We also administered doxorubicin in mice lacking p53 in the liver and in two human hepatic cells lines (HepG2 and THLE2. Results: The attenuation of liver damage was accompanied by the stimulation of fatty acid oxidation and decrease of lipogenesis, inflammation, and ER stress. The effects of doxorubicin were abrogated in mice with liver-specific ablation of p53. Finally, the effects of doxorubicin on lipid metabolism found in animal models were also present in two human hepatic cells lines, in which the drug stimulated fatty acid oxidation and inhibited de novo lipogenesis at doses that did not cause changes in apoptosis or cell viability. Conclusion: These data provide new evidence for targeting p53 as a strategy to treat liver disease. Keywords: Obesity, Lipid metabolism, Inflammation

  2. Bicontinuous cubic liquid crystalline nanoparticles for oral delivery of Doxorubicin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present study explores the potential of bicontinous cubic liquid crystalline nanoparticles (LCNPs) for improving therapeutic potential of doxorubicin. METHODS: Phytantriol based Dox-LCNPs were prepared using hydrotrope method, optimized for various formulation components, process...

  3. Protolichesterinic acid enhances doxorubicin-induced apoptosis in HeLa cells in vitro.

    Science.gov (United States)

    Brisdelli, Fabrizia; Perilli, Mariagrazia; Sellitri, Doriana; Bellio, Pierangelo; Bozzi, Argante; Amicosante, Gianfranco; Nicoletti, Marcello; Piovano, Marisa; Celenza, Giuseppe

    2016-08-01

    The aim of this study was to investigate the effect of protolichesterinic acid, a lichen secondary metabolite, on anti-proliferative activity of doxorubicin in three human cancer cell lines, HeLa, SH-SY5Y and K562 cells. The data obtained from MTT assays, performed on cells treated with protolichesterinic acid and doxorubicin alone and in combination, were analysed by the median-effect method as proposed by Chou and Talalay and the Bliss independence model. Apoptosis rate was evaluated by fluorescence microscopy, caspase-3, 8 and 9 activities were detected by spectrofluorimetric analysis and protein expression of Bim, Bid, Bax and Mcl-2 was analysed by Western blotting. The interaction of protolichesterinic acid with thioesterase domain of human fatty acid synthase (hFAS) was investigated by a molecular docking study. The in vitro activity of doxorubicin against HeLa cancer cell line, but not against SH-SY5Y and K562 cells, was synergically increased by protolichesterinic acid. The increased cytotoxicity caused by protolichesterinic acid in HeLa cells was due to a pro-apoptotic effect and was associated to caspase-3, 8 and 9 activation. The simultaneous treatment for 24h with protolichesterinic acid plus doxorubicin caused an increase of Bim protein expression and the appearance of cleaved form of Bid protein. The molecular modelling analysis showed that protolichesterinic acid seemed to behave as a competitive inhibitor of hFAS. These results suggest that protolichesterinic acid could be envisaged as an useful tool against certain types of tumor cells in combination with anticancer drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Involvement of HIF-1α activation in the doxorubicin resistance of human osteosarcoma cells.

    Science.gov (United States)

    Roncuzzi, Laura; Pancotti, Fabia; Baldini, Nicola

    2014-07-01

    Osteosarcoma is the most common primary bone cancer in children and adolescents. Despite aggressive treatment regimens, survival outcomes remain unsatisfactory, particularly in patients with metastatic and/or recurrent disease. Unfortunately, treatment failure is commonly due to the development of chemoresistance, for which the underlying molecular mechanisms remain unclear. The aim of the present study was to investigate the role of hypoxia-inducible factor 1α (HIF‑1α) and its signalling pathways as mediators of drug-resistance in human osteosarcoma. Toward this aim, we established two osteosarcoma cell lines selected for resistance to doxorubicin, a drug of choice in the treatment of this tumour. Our results showed that the multidrug resistance (MDR) phenotype was also mediated by HIF-1α, the most important regulator of cell adaptation to hypoxia. Our data showed that this transcription factor promoted the outward transport of intracellular doxorubicin by activating the P-glycoprotein (P-gp) expression in osteosarcoma cells maintained in normoxic conditions. In addition, it hindered doxorubicin-induced apoptosis by regulating the expression of c-Myc and p21. Finally, we observed that the doxorubicin-resistant cells maintained for 2 months of continuous culture in a drug-free medium, lost their drug-resistance and this effect was associated with the absence of HIF-1α expression. The emerging role of HIF-1α in osteosarcoma biology indicates its use as a valuable therapeutic target.

  5. One electron reduction and absorption characteristics of Cresyl violet in micellar medium

    International Nuclear Information System (INIS)

    Gawandi, Vijay B.; Guha, S.N.; Hari Mohan

    2000-01-01

    Effect of surfactant micelles on absorption characteristics of Cresyl violet (CV) and on its redox reactions have been studied. Among the various surfactants investigated anionic surfactants particularly sodium lauryl sulfate (SLS) and sodium dodecyl benzene sulfonate (SDDBS) showed marked effect on these properties. Reactions of hydrated electron in these micellar media were studied using the technique of nanosecond pulse radiolysis. Results of other surfactants, viz.BSS, CTAB and TritonX-100 have also been presented. (author)

  6. Antitumor Properties of Modified Detonation Nanodiamonds and Sorbed Doxorubicin on the Model of Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Medvedeva, N N; Zhukov, E L; Inzhevatkin, E V; Bezzabotnov, V E

    2016-01-01

    We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds.

  7. Strontium-rubidium infusion pump with in-line dosimetry

    International Nuclear Information System (INIS)

    Barker, S.L.; Loberg, M.D.

    1986-01-01

    A strontium-rubidium infusion system is described which consists of: (a) means for generating rubidium 82 in a solution which can be infused into a patient; (b) means for infusing the solution into a patient; (c) means for measuring the radioactivity present in the solution as it is infused into the patient; and (d) means for controlling the means for infusing in response to the amount of radioactivity which has been infused into the patient

  8. Micellar polymerization: Computer simulations by dissipative particle dynamics.

    Science.gov (United States)

    Shupanov, Ruslan; Chertovich, Alexander; Kos, Pavel

    2018-07-15

    Nowadays, micellar polymerization is widely used in different fields of industry and research, including modern living polymerization technique. However, this process has many variables and there is no comprehensive model to describe all features. This research presents simulation methodology which describes key properties of such reactions to take a guide through a variety of their modifications. Dissipative particle dynamics is used in addition to Monte Carlo scheme to simulate initiation, propagation, and termination events. Influence of initiation probability and different termination processes on final conversion and molecular-weight distribution are presented. We demonstrate that prolonged initiation leads to increasing in polymer average molecular weight, and surface termination events play major role in conversion limitation, in comparison with recombination. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  9. Safety and efficacy of pegylated liposomal doxorubicin in HIV-associated Kaposi’s sarcoma

    Directory of Open Access Journals (Sweden)

    Francesca Cainelli

    2009-08-01

    Full Text Available Francesca Cainelli1, Alfredo Vallone21Department of Internal Medicine, School of Medicine, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana; 2Infectious Diseases Unit, Annunziata Hospital, Cosenza, ItalyAbstract: Kaposi’s sarcoma is a vascular tumor linked to the presence of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8 and the incidence of which has increased considerably the world over after the onset of the human immunodeficiency virus (HIV pandemic. Antiretroviral therapy combined with cytotoxic agents has been established as the treatment of choice in the past 10 years. Among chemotherapeutic agents, pegylated liposomal doxorubicin has become the preferred one for patients with HIV-associated Kaposi’s sarcoma in Western countries. The drug in this formulation localizes better to the tumor and has higher efficacy. Skin toxicity, mucositis, and leukopenia/neutropenia are the main side effects. Hepatotoxicity and mild cardiotoxicity are observed less frequently. Pegylated liposomal doxorubicin impacts favorably on quality of life. Although cost effective in Western countries, the drug is less so in developing countries.Keywords: pegylated liposomal doxorubicin, Kaposi’s sarcoma, HIV infection

  10. Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma.

    Science.gov (United States)

    Malarvizhi, Giridharan Loghanathan; Retnakumari, Archana Payickattu; Nair, Shantikumar; Koyakutty, Manzoor

    2014-11-01

    Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing >75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in ~92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer. Transferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The U.S. home infusion market.

    Science.gov (United States)

    Monk-Tutor, M R

    1998-10-01

    Medicare legislation stimulated the development of home care services but also resulted in fragmentation of service components. In the 1980s, prospective pricing and diagnosis-related groups, and resulting pressures to reduce inpatient length of stay, prompted additional growth of the industry. Even so, in 1995 home care represented only 3% of total national expenditures on health care. The annual growth rate of the home infusion industry dropped from 64% in 1982-86 to 24% in 1986-93. While revenue per patient for home infusion is expected to decrease under managed care, an increasing number of patients will support continued market growth. The home infusion market is highly competitive, with only a few large national providers and many small local providers. In 1996, 29% of acute care hospitals provided or were developing a home care program. Community pharmacists' options in the home infusion area include independent services, partnerships, joint ventures, contracts with hospitals, and franchises. The home infusion market is being integrated into alternative sites, such as ambulatory infusion centers (AICs), as providers attempt to diversify to maintain managed care contracts. AICs provide infusion therapy and nursing to noninstitutionalized, nonhome-bound patients. Untapped sources for future growth of the infusion market include long-term-care facilities. More consistent studies of the home care market are needed. Despite slowed growth in recent years, home care has a strong market in the United States.

  12. Structural study of concentrated micellar solutions

    International Nuclear Information System (INIS)

    Zemb, Thomas

    1985-01-01

    This research thesis reports the study of the structure of concentrated soap-water binary micelles with a comparison of measurements of light, neutrons and X-ray scattering, and the relaxation induced by paramagnetic ions adsorbed at the interface. In the first part, the author discusses the specific sensitivity ranges of different experimental techniques, outlines the resolution which can be obtained with scattering experiments, and proposes a critical analysis of results published in the relevant literature. In a second part, the author discusses the compared results of the application of various techniques (magnetic resonance, X-light and neutron scattering) on the two most used model systems: sodium octanoate and sodium dodecyl sulfate (SDS) in solution. Then, the author addresses the case of ternary systems: study of the influence of the presence of a co-surfactant on the structure, study of the effect of interfacial charge on the micellar structure, use of the same previous quantitative methods to study the disturbances brought to the structure due to the presence of reactants [fr

  13. Targeting PEPT1: a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy.

    Science.gov (United States)

    Gong, Yanxia; Wu, Xiang; Wang, Tao; Zhao, Jia; Liu, Xi; Yao, Zhi; Zhang, Qingyu; Jian, Xu

    2017-06-20

    Proton coupled oligopeptide transporter 1 (PEPT1) is a member of the peptide transporter superfamily and plays important role in the absorption of oligopeptide and peptidomimetic drugs. Our previous research verified that PEPT1 expressed specifically in human Hepatocellular carcinoma (HCC) tissue and cell lines and showed potential transport activity to be a new candidate of the tumor therapeutic target. In this study, we aim to explore the feasibility of a novel tumor target therapeutic strategy: Targeting PEPT1 to improve the antitumor efficacy of Doxorubicin in human HCC therapy. First, Doxorubicin was conjugated with Glycylglycylglycine (Gly-Gly-Gly) - a tripeptide which was known as the substrate of PEPT1 and characterized by HPLC and MS successfully. Doxorubicin-tripeptide conjugate was then observed to clarify the target delivery by PEPT1 and the antitumor effect on human hepatocarcinoma in vivo and in vitro. Furthermore, the improvement of the toxic and side effect of Doxorubicin after conjugation was also evaluated by some biochemical tests. Our results reveal that targeting PEPT1 may contribute to the efficient delivery of Doxorubicin to hepatocarcinoma cells and the reduction of drug toxicity. PEPT1 has the prospect to be a novel target of HCC therapy.

  14. Multicompartment micellar aggregates of linear ABC amphiphiles in solvents selective for the C block: A Monte Carlo simulation

    KAUST Repository

    Zhu, Yutian; Yu, Haizhou; Wang, Yongmei; Cui, Jie; Kong, Weixin; Jiang, Wei

    2012-01-01

    the simulations and the detailed phase diagrams for the ABC amphiphiles with different block lengths are obtained. The simulation results reveal that the micellar structure is largely controlled by block length, solvent quality, and incompatibility between

  15. Synergistic effect of pyrazoles derivatives and doxorubicin in claudin-low breast cancer subtype.

    Science.gov (United States)

    Saueressig, Silvia; Tessmann, Josiane; Mastelari, Rosiane; da Silva, Liziane Pereira; Buss, Julieti; Segatto, Natalia Vieira; Begnini, Karine Rech; Pacheco, Bruna; de Pereira, Cláudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

    2018-02-01

    Breast cancer is a global public health problem. For some subtypes, such as Claudin-low, the prognosis is poorer and the treatment is still a challenge. Pyrazoles are an important class of heterocyclic compounds and are promising anticancer agents based on their chemical properties. The present study was aimed not only at testing pyrazoles previously prepared by our research group in two breast cancer cell lines characterized by intermediated response to conventional chemotherapy but also at analyzing the possible synergistic effect of these pyrazoles associated with doxorubicin. Four 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H pyrazoles were tested for the first time in MCF-7 and MDA-MB-231 culture cells. The pyrazoles with best results in cytotoxicity were used in combination with doxorubicin and compared with this drug alone as standard. The synergic effect was analyzed using Combination Index method. In addition, cell death and apoptosis assays were carried out. Two pyrazoles with cytotoxic effect in MCF-7 and especially in MDA-MB-231 were identified. This activity was markedly higher in pyrazoles containing bromine and chlorine substituents. The combination of these pyrazoles with doxorubicin had a significant synergic effect in both cells tested and mainly in MDA-MB-231. These data were confirmed with apoptosis and cell death analysis. The synergic effect observed with combination of these pyrazoles and doxorubicin deserves special attention in Claudin-low breast cancer subtype. This should be explored in order to improve treatment results and minimize side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Dynamic and structural characterisation of micellar solutions of surfactants by spin relaxation and translational diffusion

    International Nuclear Information System (INIS)

    Mahieu, Nathalie

    1992-01-01

    The work reported in this research thesis aimed at characterizing micellar phases formed by some surfactants (sodium carboxylates) in aqueous solution. After some recalls on nuclear magnetic resonance dealing with spin relaxation (longitudinal relaxation, transverse relaxation, relaxation in the rotating coordinate system, and crossed relaxation), and comments on the dipolar mechanism responsible of relaxation phenomena, the author presents the methods used for relaxation parameter measurement and the data processing software issued from experiments. He presents experiments which allowed the self-diffusion coefficient to be measured, reports data processing, and addresses problems of special diffusion and of coherence transfers during diffusion measurements. Results of proton relaxation measurements are then presented and discussed. They are used to determine the micellar state of the studied carboxylates. The case of the oleate is also addressed. Measurements of carbon-13 relaxation times are reported, and exploited in terms of structural parameters by using the Relaxator software. An original method of the hetero-nuclear Overhauser method is presented, and used to assess the average distance between water molecules and micelle surface [fr

  17. Early mechanism of action of arterially infused ethanol: an experimental study on the influence of infusion speed

    International Nuclear Information System (INIS)

    Han, Joon Koo

    1988-01-01

    Abdominal aortography and histopathologic examination after absolute ethanol infusion at fast (0.4cc/sec) and slow speed (0.04cc/sec) were performed on 16 rats (2 controls. 7 fast infusion group. 7 slow infusion group). Angiographic and histopathologic findings were correlated and the findings of slow and fast infusion groups were studied. The results are as follows: 1. Histopathologic findings of the fast infusion group revealed wide area of glomerular and tubular collapses, obliteration of the free space between the Bowmann's capsule and glomerulus, sloughing and loss of the endothelium, fresh thrombi attached to the wall, and cleavage of the muscle layer of the arteries. 2. Angiographic findings of the fast infusion group revealed luminal irregularity, early obstruction of the aorta and the renal arteries, and delayed circulation time. 3. Histopathologic findings of the slow infusion group revealed degenerated, coalesced red blood cell packed in the glomeruli, focal areas of severe glomerular and tubular damage on relatively normal background, endothelial and muscular damage of the arteries. 4. Angiographic findings of the slow infusion group revealed focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but there was no obstruction of the major arteries. 5. In conclusion, author believes that endothelial damage and thrombus formation from the damaged vessel wall, as well as direct cytotoxicity and in situ emboli formation play a significant role in the embolic effect of absolute ethanol.

  18. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Combined doxorubicin and paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    -550). The main toxicities were neutropenia, parestesia, nausea/vomiting, alopecia, myalgia and cardiotoxicity. Fifteen patients (50%) had reductions of left ventricular ejection fraction of below normal levels and 6 of these patients (20%) developed congestive heart failure. CONCLUSION: The combination...... of doxorubicin and paclitaxel is highly active, but is accompanied by the dose-limiting toxic effects of neutropenia, neuropathy and cardiotoxicity....

  20. Spectroscopic Behavior of Some A3B Type Tetrapyrrolic Complexes in Several Organic Solvents and Micellar Media

    Directory of Open Access Journals (Sweden)

    Radu Socoteanu

    2011-08-01

    Full Text Available The paper presents spectral studies of some unsymmetrical A3B tetrapyrrolic, porphyrin-type complexes with Cu(II and Zn(II in different solvents and micellar media aimed at estimating their properties in connection with the living cell. The results indicate that the position of the absorption and emission peaks is mostly influenced by the central metal ion and less by the environmental polarity or the peripheric substituents of the porphyrinic core. The comparison between the overall absorption and emission spectra of the compounds in methanol or cyclohexane vs. direct and reverse Triton X micellar systems, respectively, suggests for all compounds the localization at the interface between the polyethylene oxide chains and the tert-octyl-phenyl etheric residue of the Triton X-100 molecules. These findings could be important when testing the compounds embedded in liposomes or other delivery systems to the targeted cell.

  1. Chiral separation of amino acids in biological fluids by micellar electrokinetic chromatography with laser-induced fluorescence detection.

    Science.gov (United States)

    Thorsén, G; Bergquist, J

    2000-08-18

    A method is presented for the chiral analysis of amino acids in biological fluids using micellar electrokinetic chromatography (MEKC) and laser-induced fluorescence (LIF). The amino acids are derivatized with the chiral reagent (+/-)-1-(9-anthryl)-2-propyl chloroformate (APOC) and separated using a mixed micellar separation system. No tedious pre-purification of samples is required. The excellent separation efficiency and good detection capabilities of the MEKC-LIF system are exemplified in the analysis of urine and cerebrospinal fluid. This is the first time MEKC has been reported for chiral analysis of amino acids in biological fluids. The amino acids D-alanine, D-glutamine, and D-aspartic acid have been observed in cerebrospinal fluid, and D-alanine and D-glutamic acid in urine. To the best of our knowledge no measurements of either D-alanine in cerebrospinal fluid or D-glutamic acid in urine have been presented in the literature before.

  2. 21 CFR 880.5725 - Infusion pump.

    Science.gov (United States)

    2010-04-01

    ... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and...

  3. Effect of doxorubicin/pluronic SP1049C on tumorigenicity, aggressiveness, DNA methylation and stem cell markers in murine leukemia.

    Directory of Open Access Journals (Sweden)

    Daria Y Alakhova

    Full Text Available Pluronic block copolymers are potent sensitizers of multidrug resistant cancers. SP1049C, a Pluronic-based micellar formulation of doxorubicin (Dox has completed Phase II clinical trial and demonstrated safety and efficacy in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction. This study elucidates the ability of SP1049C to deplete cancer stem cells (CSC and decrease tumorigenicity of cancer cells in vivo.P388 murine leukemia ascitic tumor was grown in BDF1 mice. The animals were treated with: (a saline, (b Pluronics alone, (c Dox or (d SP1049C. The ascitic cancer cells were isolated at different passages and examined for 1 in vitro colony formation potential, 2 in vivo tumorigenicity and aggressiveness, 3 development of drug resistance and Wnt signaling activation 4 global DNA methylation profiles, and 5 expression of CSC markers.SP1049C treatment reduced tumor aggressiveness, in vivo tumor formation frequency and in vitro clonogenic potential of the ascitic cells compared to drug, saline and polymer controls. SP1049C also prevented overexpression of BCRP and activation of Wnt-β-catenin signaling observed with Dox alone. Moreover, SP1049C significantly altered the DNA methylation profiles of the cells. Finally, SP1049C decreased CD133(+ P388 cells populations, which displayed CSC-like properties and were more tumorigenic compared to CD133(- cells.SP1049C therapy effectively suppresses the tumorigenicity and aggressiveness of P388 cells in a mouse model. This may be due to enhanced activity of SP1049C against CSC and/or altered epigenetic regulation restricting appearance of malignant cancer cell phenotype.

  4. Photochemical assessment of UO2+2 complexation in Triton X-100 micellar system

    International Nuclear Information System (INIS)

    Das, S.K.; Ganguly, B.N.

    1994-01-01

    This is a report on the spectral characteristics of UO 2 +2 in the excited state in the Triton X-100 micellar medium. The downward curving of the Stern-Volmer plot explains the two kinds of populations of UO 2 +2 upon micellization. A blue shift of the quenched emission is ascribed due to the collisional encounter of UO 2 +2 with the head groups of Triton X-100. (author). 5 refs., 2 figs

  5. Surface dynamics of micellar diblock copolymer films

    Science.gov (United States)

    Song, Sanghoon; Cha, Wonsuk; Kim, Hyunjung; Jiang, Zhang; Narayanan, Suresh

    2011-03-01

    We studied the structure and surface dynamics of poly(styrene)-b-poly(dimethylsiloxane) (PS-b-PDMS) diblock copolymer films with micellar PDMS surrounded by PS shells. By `in-situ' high resolution synchrotron x-ray reflectivity and diffuse scattering, we obtained exact thickness, electron density and surface tension. A segregation layer near the top surface was appeared with increasing temperature Surface dynamics were measured as a function of film thickness and temperature by x-ray photon correlation spectroscopy. The best fit to relaxation time constants as a function of in-plane wavevectors were analyzed with a theory based on capillary waves with hydrodynamics with bilayer model Finally the viscosities for the top segregated layer as well as for the bottom layer are obtained at given temperatures This work was supported by National Research Foundation of Korea (R15-2008-006-01001-0), Seoul Research and Business Development Program (10816), and Sogang University Research Grant (2010).

  6. pH-Switch Nanoprecipitation of Polymeric Nanoparticles for Multimodal Cancer Targeting and Intracellular Triggered Delivery of Doxorubicin.

    Science.gov (United States)

    Herranz-Blanco, Bárbara; Shahbazi, Mohammad-Ali; Correia, Alexandra R; Balasubramanian, Vimalkumar; Kohout, Tomáš; Hirvonen, Jouni; Santos, Hélder A

    2016-08-01

    Theranostic nanoparticles are emerging as potent tools for noninvasive diagnosis, treatment, and monitoring of solid tumors. Herein, an advanced targeted and multistimuli responsive theranostic platform is presented for the intracellular triggered delivery of doxorubicin. The system consists of a polymeric-drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles (IO@PNP) and decorated with a tumor homing peptide, iRGD. The production of this nanosystem is based on a pH-switch nanoprecipitation method in organic-free solvents, making it ideal for biomedical applications. The nanosystem shows sufficient magnetization saturation for magnetically guided therapy along with reduced cytotoxicity and hemolytic effects. IO@PNP are largely internalized by endothelial and metastatic cancer cells and iRGD decorated IO@PNP moderately enhance their internalization into endothelial cells, while no enhancement is found for the metastatic cancer cells. Poly(ethylene glycol)-block-poly(histidine) with pH-responsive and proton-sponge properties promotes prompt lysosomal escape once the nanoparticles are endocyted. In addition, the polymer-doxorubicin conjugate solid nanoparticles show both intracellular lysosomal escape and efficient translocation of doxorubicin to the nuclei of the cells via cleavage of the amide bond. Overall, IO@PNP-doxorubicin and the iRGD decorated counterpart demonstrate to enhance the toxicity of doxorubicin in cancer cells by improving the intracellular delivery of the drug carried in the IO@PNP. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Early biomarkers of doxorubicin-induced heart injury in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Kwekel, Joshua C.; Vijay, Vikrant; Moland, Carrie L. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Herman, Eugene H. [Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850-9734 (United States); Lee, Taewon [Department of Mathematics, Korea University, Sejong, Chungnam 339-700 (Korea, Republic of); Han, Tao [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Davis, Kelly J.; Muskhelishvili, Levan [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Kerr, Susan [Arkansas Heart Hospital, Little Rock, AR 72211 (United States); Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2014-12-01

    Cardiac troponins, which are used as myocardial injury markers, are released in plasma only after tissue damage has occurred. Therefore, there is a need for identification of biomarkers of earlier events in cardiac injury to limit the extent of damage. To accomplish this, expression profiling of 1179 unique microRNAs (miRNAs) was performed in a chronic cardiotoxicity mouse model developed in our laboratory. Male B6C3F{sub 1} mice were injected intravenously with 3 mg/kg doxorubicin (DOX; an anti-cancer drug), or saline once a week for 2, 3, 4, 6, and 8 weeks, resulting in cumulative DOX doses of 6, 9, 12, 18, and 24 mg/kg, respectively. Mice were euthanized a week after the last dose. Cardiac injury was evidenced in mice exposed to 18 mg/kg and higher cumulative DOX dose whereas examination of hearts by light microscopy revealed cardiac lesions at 24 mg/kg DOX. Also, 24 miRNAs were differentially expressed in mouse hearts, with the expression of 1, 1, 2, 8, and 21 miRNAs altered at 6, 9, 12, 18, and 24 mg/kg DOX, respectively. A pro-apoptotic miR-34a was the only miRNA that was up-regulated at all cumulative DOX doses and showed a significant dose-related response. Up-regulation of miR-34a at 6 mg/kg DOX may suggest apoptosis as an early molecular change in the hearts of DOX-treated mice. At 12 mg/kg DOX, up-regulation of miR-34a was associated with down-regulation of hypertrophy-related miR-150; changes observed before cardiac injury. These findings may lead to the development of biomarkers of earlier events in DOX-induced cardiotoxicity that occur before the release of cardiac troponins. - Highlights: • Upregulation of miR-34a before doxorubicin-induced cardiac tissue injury • Apoptosis might be an early event in mouse heart during doxorubicin treatment. • Expression of miR-150 declined before doxorubicin-induced cardiac tissue injury.

  8. Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer.

    Science.gov (United States)

    Semkina, Alevtina S; Abakumov, Maxim A; Skorikov, Alexander S; Abakumova, Tatiana O; Melnikov, Pavel A; Grinenko, Nadejda F; Cherepanov, Sergey A; Vishnevskiy, Daniil A; Naumenko, Victor A; Ionova, Klavdiya P; Majouga, Alexander G; Chekhonin, Vladimir P

    2018-05-03

    In presented paper we have developed new system for cancer theranostics based on vascular endothelial growth factor (VEGF) targeted magnetic nanoparticles. Conjugation of anti-VEGF antibodies with bovine serum albumin coated PEGylated magnetic nanoparticles allows for improved binding with murine breast adenocarcinoma 4T1 cell line and facilitates doxorubicin delivery to tumor cells. It was shown that intravenous injection of doxorubicin loaded VEGF targeted nanoparticles increases median survival rate of mice bearing 4T1 tumors up to 50%. On the other hand magnetic resonance imaging (MRI) of 4T1 tumors 24 h after intravenous injection showed accumulation of nanoparticles in tumors, thus allowing simultaneous cancer therapy and diagnostics. Copyright © 2018. Published by Elsevier Inc.

  9. [A Case of HPN, In Which QOL Improvement Was Achieved by Combining Continuous Infusion with Once-Weekly Intermittent Infusion - Contribution of Pharmacists to Health Promotion among Home Patients Receiving Infusion Therapy].

    Science.gov (United States)

    Takeda, Namihiro; Hamana, Tomoko; Oka, Toyoka; Hirohara, Masayoshi; Kushida, Kazuki

    2016-12-01

    Patients receiving parenteral nutrition at home have the following two options: 24-h continuous or intermittent infusion. To date, for patients with impaired glucose tolerance and/or other metabolic disorders or for those with decreased cardiac/ pulmonary/renal function, it is desirable to opt for continuous infusion to minimize the variance in the body's metabolic rate as much as possible. Furthermore, it should be noted that continuous infusion evokes a stronger feeling among patients of being constrained because it restricts their everyday activities. This case witnesses collaborations among the patient's doctor, dispensary's pharmacy, and patient's family. Because ofthe use ofintermittent infusion more or less once per week in addition to continuous infusion, significant improvement in quality of life was achieved, and the patient was able to enjoy taking a short trip. To assist a home patient receiving infusion therapy, it is essential that the pharmacist be equipped with skills to manage risks associated with infusion therapy and have knowledge about insurance to cover incidents concerning infusion fluids or medical materials. It will certainly depend on the degree ofindependence ofpatients and the level ofcare their families can provide; however, should we manage to use a similar medical procedure in at least a few cases in the future, we may be able to contribute to "joie de vivre" in home patients receiving infusion therapy.

  10. Sleep pattern and locomotor activity are impaired by doxorubicin in non-tumor-bearing rats.

    Science.gov (United States)

    Lira, Fabio Santos; Esteves, Andrea Maculano; Pimentel, Gustavo Duarte; Rosa, José Cesar; Frank, Miriam Kannebley; Mariano, Melise Oliveira; Budni, Josiane; Quevedo, João; Santos, Ronaldo Vagner Dos; de Mello, Marco Túlio

    2016-01-01

    We sought explore the effects of doxorubicin on sleep patterns and locomotor activity. To investigate these effects, two groups were formed: a control group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control or DOXO groups. The sleep patterns were examined by polysomnographic recording and locomotor activity was evaluated in an open-field test. In the light period, the total sleep time and slow wave sleep were decreased, while the wake after sleep onset and arousal were increased in the DOXO group compared with the control group (plocomotor activity.

  11. Chemiluminescence from an oxidation reaction of rhodamine B with cerium(IV) in a reversed micellar medium of cetyltrimethylammonium chloride in 1-hexanol-cyclohexane/water.

    Science.gov (United States)

    Hasanin, Tamer H A; Tsunemine, Yusuke; Tsukahara, Satoshi; Okamoto, Yasuaki; Fujiwara, Terufumi

    2011-01-01

    The chemiluminescence (CL) emission, observed when rhodamine B (RB) in 1-hexanol-cyclohexane was mixed with cerium(IV) sulfate in sulfuric acid dispersed in a reversed micellar medium of cetyltrimethylammonium chloride (CTAC) in 1-hexanol-cyclohexane/water, was investigated using a flow-injection system. The CL emission from the oxidation reaction of RB with Ce(IV) was found to be stronger in the CTAC reversed micellar solution compared with an aqueous solution. Bearing on the enhancement effect of the CTAC reverse micelles on the RB-Ce(IV) CL, several studies including stopped-flow, fluorescence and electron spin resonance (ESR) spectrometries were performed. Rapid spectral changes of an intermediate in the RB-Ce(IV) reaction in the aqueous and reversed micellar solutions were successfully observed using a stopped-flow method. The effect of the experimental variables, i.e., oxidant concentration, sulfuric acid concentration, the mole fraction of 1-hexanol, water-to-surfactant molar concentration ratio, flow rate, upon the CL intensity was evaluated. Under the experimental conditions optimized for a flow-injection determination of RB based on the new reversed micellar-mediated CL reaction with Ce(IV), a detection limit of 0.08 µmol dm(-3) RB was achieved, and a linear calibration graph was obtained with a dynamic range from 0.5 to 20 µmol dm(-3). The relative standard deviation (n = 6) obtained at an RB concentration of 3 µmol dm(-3) was 3%.

  12. Retrospective evaluation of doxorubicin-piroxicam combination for the treatment of transitional cell carcinoma in dogs.

    Science.gov (United States)

    Robat, C; Burton, J; Thamm, D; Vail, D

    2013-02-01

    To determine whether doxorubicin-piroxicam combination is safe and has activity against transitional cell carcinoma in dogs. Data was collected retrospectively from 34 dogs from two institutions over a 6-year period. Signalment, clinical presentation, treatment specifics, adverse events, response, progression-free survival and overall survival time were evaluated. Dogs received doxorubicin every 3 weeks and daily piroxicam; 17 dogs (50%) had surgery. Clinical presentations were those typically reported for transitional cell carcinoma. Mean number of doses administered was 3·5. Of the 23 dogs with measurable disease, 14 (60·5%) had stable disease, 7 (30·5%) had progressive disease and 2 (9%) a partial response. Adverse events were generally manageable, and gastrointestinal in origin; one dog died of treatment-related complications. Overall median progression-free survival and overall survival were 103 and 168 days, respectively. Cytoreductive surgery did not result in prolongation of progression-free survival, but significantly prolonged overall survival. All dogs but one died as a result of disease progression. Doxorubicin-piroxicam combination therapy is well-tolerated in dogs with transitional cell carcinoma although progression-free survival, overall survival and biological response rates appear modest. Combination with surgery appears to offer a survival advantage; however, this may reflect tumour location and volume. Prospective studies are necessary to compare activity of combination doxorubicin-piroxicam to currently applied therapies. © 2013 British Small Animal Veterinary Association.

  13. Analysis of micellar and vesicular lecithin and cholesterol in model bile using 1H- and 31P-NMR

    NARCIS (Netherlands)

    de Graaf, M. P.; Groen, A. K.; Bovée, W. M.

    1995-01-01

    The distribution of phospholipid and cholesterol between the vesicular and micellar phases in bile plays an important role in the formation of cholesterol gallstones. Conventional analytical procedures to determine the distribution are potentially unreliable because they disturb the distribution of

  14. Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number.

    Science.gov (United States)

    Wasserman, Michael J; Weber, Deborah A; Guthrie, Judith A; Bykerk, Vivian P; Lee, Peter; Keystone, Edward C

    2004-10-01

    We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.

  15. Technical note: Development and validation of a new method for the quantification of soluble and micellar calcium, magnesium, and potassium in milk.

    Science.gov (United States)

    Franzoi, M; Niero, G; Penasa, M; Cassandro, M; De Marchi, M

    2018-03-01

    Milk mineral content is a key trait for its role in dairy processes such as cheese-making, its use as source of minerals for newborns, and for all traits involving salt-protein interactions. This study investigated a new method for measuring mineral partition between soluble and micellar fractions in bovine milk after rennet coagulation. A new whey dilution step was added to correct the quantification bias due to whey trapped in curd and excluded volume. Moreover, the proposed method allowed the quantification of the diffusible volume after milk coagulation. Milk mineral content and concentration in whey, and diluted whey were quantified by acid digestion and inductively coupled plasma optical emission spectrometry. The repeatability of the method for micellar Ca, Mg, and K was between 2.07 and 8.96%, whereas reproducibility ranged from 4.01 to 9.44%. Recovery of total milk minerals over 3 spiking levels ranged from 92 to 97%. The proposed method provided an accurate estimation of micellar and soluble minerals in milk, and curd diffusible volume. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Extended infusion versus intermittent infusion of imipenem in the treatment of ventilator-associated pneumonia.

    Science.gov (United States)

    Ibrahim, Mohamed M; Tammam, Tarek Fouad; Ebaed, Mohy El Deen; Sarhan, Hatem A; Gad, Gamal F; Hussein, Amal K

    2017-01-01

    Mechanical ventilation support can be the main source of ventilator-associated pneumonia (VAP). VAP is a serious infection that may be associated with dangerous gram-negative bacteria mainly, and it leads to an increase in the mortality in the intensive care unit (ICU). Imipenem is one of the strongest antibiotics now available for treating VAP which is associated with gram-negative and gram-positive bacteria, and it belongs to beta-lactam antibiotic group (carbapenem). This study tried to investigate the efficacy of imipenem against VAP when it was infused within 180 min versus the efficacy when it was infused within 30-60 min. This study was conducted in main ICU in general hospital which consists of surgical and medical beds within 2 years. One hundred and eighty-seven patients were enrolled on it. This study is a retrospective cohort which was conducted within 2 years. The efficacy of imipenem which was administered by intermittent infusion (30-60 min) within first year was compared with the efficacy of imipenem which was administered by extended infusion (180 min) within second year in the field of VAP curing and cost reduction. All data were collected retrospectively from patient medical files and were statistically analyzed by SPSS version 20. The study was designed to measure clinical and cost reduction outcomes, mortality and hospital stay. The results indicated that there is a significant decrease in mortality, number of recurrent infection, and ICU stay length, and the number of mechanical ventilator days was associated with extended imipenem infusion during the second year of the study. The use of imipenem with extended infusion over 3 hours enhances its clinical outcomes in the treatment of VAP.

  17. Understanding Infusion Pumps.

    Science.gov (United States)

    Mandel, Jeff E

    2018-04-01

    Infusion systems are complicated electromechanical systems that are used to deliver anesthetic drugs with moderate precision. Four types of systems are described-gravity feed, in-line piston, peristaltic, and syringe. These systems are subject to a number of failure modes-occlusion, disconnection, siphoning, infiltration, and air bubbles. The relative advantages of the various systems and some of the monitoring capabilities are discussed. A brief example of the use of an infusion system during anesthetic induction is presented. With understanding of the functioning of these systems, users may develop greater comfort.

  18. Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3β pathway independent of PI3K/Akt

    International Nuclear Information System (INIS)

    He, Shu-Fang; Jin, Shi-Yun; Wu, Hao; Wang, Bin; Wu, Yun-Xiang; Zhang, Shu-Jie; Irwin, Michael G.; Wong, Tak-Ming; Zhang, Ye

    2015-01-01

    Preconditioning against myocardial ischemia–reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3β pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3β. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3β induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3β in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3β pathway independent of PI3K/Akt. - Highlights: • Morphine and ischemic preconditioning are cardioprotective in normal rat hearts. • Ischemic preconditioning fails to confer cardioprotection in rats with heart failure. • Morphine retains cardioprotection in doxorubicin-induced heart failure. • Morphine exerts cardioprotection via the ERK/GSK-β pathway independent of PI3K/Akt.

  19. Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3β pathway independent of PI3K/Akt

    Energy Technology Data Exchange (ETDEWEB)

    He, Shu-Fang; Jin, Shi-Yun; Wu, Hao; Wang, Bin; Wu, Yun-Xiang [Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601 (China); Zhang, Shu-Jie [Department of Ultrasound, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601 (China); Irwin, Michael G.; Wong, Tak-Ming [Department of Anesthesiology, University of Hong Kong (Hong Kong); Zhang, Ye, E-mail: zhangye_hassan@aliyun.com [Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601 (China)

    2015-11-01

    Preconditioning against myocardial ischemia–reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3β pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3β. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3β induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3β in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3β pathway independent of PI3K/Akt. - Highlights: • Morphine and ischemic preconditioning are cardioprotective in normal rat hearts. • Ischemic preconditioning fails to confer cardioprotection in rats with heart failure. • Morphine retains cardioprotection in doxorubicin-induced heart failure. • Morphine exerts cardioprotection via the ERK/GSK-β pathway independent of PI3K/Akt.

  20. Hypothalamic Energy Metabolism Is Impaired By Doxorubicin Independently Of Inflammation In Non-tumour-bearing Rats.

    OpenAIRE

    Antunes, Barbara M M; Lira, Fabio Santos; Pimentel, Gustavo Duarte; Rosa Neto, José Cesar; Esteves, Andrea Maculano; Oyama, Lila Missae; de Souza, Cláudio Teodoro; Gonçalves, Cinara Ludvig; Streck, Emilio Luiz; Rodrigues, Bruno; dos Santos, Ronaldo Vagner; de Mello, Marco Túlio

    2016-01-01

    We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1β, IL-6, IL-10, TNF-α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothala...

  1. Polymeric composite membranes for temperature and pH-responsive delivery of doxorubicin hydrochloride

    Directory of Open Access Journals (Sweden)

    Sahar Mohamaddoust Aliabadi

    2015-07-01

    Full Text Available Objective(s: Nowadays hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Temperature and pH-responsive delivery systems have drawn much attention because some diseases reveal themselves by a change in temperature and/or pH. The objective of this work is to prepare and characterize composite membrane using responsive nanoparticles into a polymer matrix. Materials and Methods: These nanoparticles were made of the copolymer poly (N-isopropylacrylamide-co-methaçrylic acid by an aqueous dispersion polymerization process and are responsible for dual sensitivity to temperature and pH. Morphology study with SEM, swelling behavior with Dynamic Light Scattering Technique, in vitro drug release behavior with side-by-side Diffusion Cells were also investigated in this paper. Doxorubicin hydrochloride was used as a model solute. Results:The study on the release of doxorubicin hydrochloride showed that the release rate was higher at pH 5 than pH 7.4, increased with the increase of temperature. Nevertheless, ionic strength only poses a minor direct effect at higher pH. Conclusion:Such system may be potentially used as a tumor-targeting doxorubicin hydrochloride delivery in the body.

  2. RITA enhances chemosensivity of pre-B ALL cells to doxorubicin by inducing p53-dependent apoptosis.

    Science.gov (United States)

    Kazemi, Ahmad; Safa, Majid; Shahbazi, Atefeh

    2011-07-01

    The use of low-molecular-weight, non-peptidic molecules that disrupt the interaction between the p53 tumor suppressor and its negative regulator MDM2 has provided a promising alternative for the treatment of different types of cancer. Here, we used small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) to sensitize leukemic NALM-6 cells to doxorubicin by upregulating p53 protein. RITA alone effectively inhibited NALM-6 cells viability in dose-dependent manner as measured by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay and induced apoptosis as evaluated by flow cytometry, whereas RITA in combination with doxorubicin enhanced NALM-6 cells to doxorubicin-sensitivity and promoted doxorubicin induced apoptosis. Levels of p53 protein and its proapoptotic target genes, quantified by western blot and real-time PCR respectively, showed that expression of p53 was significantly increased after RITA treatment. Using p53 inhibitors PFT-alpha and PFT-mu it was shown that p53-mediated apoptosis induced by RITA can be regulated by both p53-transcription-dependent and -independent pathways. Moreover, RITA-induced apoptosis was accompanied by the activation of caspase-3 and PARP cleavage. Therefore, exploiting synergistic effects between RITA and chemotherapeutics might be an effective clinical strategy for leukemia chemotherapy.

  3. A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery.

    Science.gov (United States)

    Yang, Conglian; Wu, Tingting; Qin, Yuting; Qi, Yan; Sun, Yu; Kong, Miao; Jiang, Xue; Qin, Xianya; Shen, Yaqi; Zhang, Zhiping

    2018-01-01

    Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor. Doxorubicin-dichloroacetate conjugate can self-assemble into nanoparticles with small amount of DSPE-PEG 2000 , leading to high drug loading (71.8%, w/w) and diminished excipient associated concerns. The nanoparticles exhibited invisible systemic toxicity and high maximum tolerated dose of 75 mg DOX equiv./kg, which was 15-fold higher than that of free DOX. It also showed good tumor targeting capability and enhanced antitumor efficacy in murine melanoma model. This work provides a promising strategy to simplify the drug preparation process, increase drug loading content, reduce systemic toxicity as well as enhance antitumor efficiency.

  4. Comparative cytotoxicity of gold-doxorubicin and InP-doxorubicin conjugates.

    Science.gov (United States)

    Zhang, Xuan; Chibli, Hicham; Kong, Dekun; Nadeau, Jay

    2012-07-11

    Direct comparisons of different types of nanoparticles for drug delivery have seldom been performed. In this study we compare the physical properties and cellular activity of doxorubicin (Dox) conjugates to gold nanoparticles (Au) and InP quantum dots of comparable diameter. Although the Au particles alone are non-toxic and InP is moderately toxic, Au-Dox is more effective than InP-Dox against the Dox-resistant B16 melanoma cell line. Light exposure does not augment the efficacy of InP-Dox, suggesting that conjugates are breaking down. Electron and confocal microscopy and atomic absorption spectroscopy reveal that over 60% of the Au-Dox conjugates reach the cell nucleus. In contrast, InP-Dox enters cell nuclei to a very limited extent, although liberated Dox from the conjugates does eventually reach the nucleus. These observations are attributed to faster Dox release from Au conjugates under endosomal conditions, greater aggregation of InP-Dox with cytoplasmic proteins, and adherence of InP to membranes. These findings have important implications for design of active drug-nanoparticle conjugates.

  5. Swelling and infusion of tea in tea bags.

    Science.gov (United States)

    Yadav, Geeta U; Joshi, Bhushan S; Patwardhan, Ashwin W; Singh, Gurmeet

    2017-07-01

    The present study deals with swelling and infusion kinetics of tea granules in tea bags. The swelling and infusion kinetics of tea bags differing in tea loading and tea bag shapes were compared with loose tea. Increment in temperature and dipping frequency of tea bag in hot water increased the infusion kinetics of tea bags. Reduction in particle size enhanced the swelling and infusion kinetics of tea in a tea bag. The effects of tea particle size, tea bag dipping rate, loading of tea granules in tea bag and tea bag shapes on infusion kinetics were investigated. Increase in tea loading in tea bags resulted in reduced infusion kinetics. Double chambered tea bag showed the highest swelling (30%) and infusion kinetics (8.30% Gallic acid equivalence) while single chambered tea bags showed the lowest kinetics, amongst the various bags studied. The swelling and infusion kinetics of loose tea was always faster and higher than that of tea bags. It was found that overall effect of percentage filling of tea granules and height of tea bed in a tea bag affects tea infusion kinetics the most. Weibull model was found to be in good agreement with the swelling data.

  6. Spectroscopic and molecular modeling study on the interaction of ctDNA with 3′-deoxy-3′-azido doxorubicin

    International Nuclear Information System (INIS)

    Geng, Shaoguang; Cui, Yanrui; Liu, Qingfeng; Cui, Fengling; Zhang, Guisheng; Chi, Yanwei; Peng, Hao

    2013-01-01

    The method of synthesizing 3′-deoxy-3′-azido doxorubicin (ADOX) directly from doxorubicin has been developed. This study presents the interaction between ADOX and calf thymus deoxyribonucleic acid (ctDNA) by using spectroscopic methods and molecular modeling techniques. Iodide quenching, fluorescence polarization, viscosity and molecular modeling studies of ADOX–ctDNA interactions indicated that ADOX was an intercalator of ctDNA and preferentially bound to C–G rich regions of ctDNA. Simultaneously, spectroscopic results indicated that the quenching mechanism of ADOX–ctDNA was a static quenching. According to thermodynamic parameters, electrostatic force played roles in the interaction of ADOX with ctDNA. -- Highlights: ●An approach to 3′-deoxy-3′-azido doxorubicin (ADOX) from doxorubicin was developed. ●The quenching mechanism of ADOX with ctDNA was a static quenching type. ●The binding mode between ADOX and ctDNA was intercalative binding. ●The results of molecular docking corroborated results of spectra investigations

  7. TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity.

    Science.gov (United States)

    Kleiner, Yana; Bar-Am, Orit; Amit, Tamar; Berdichevski, Alexandra; Liani, Esti; Maor, Gila; Reiter, Irina; Youdim, Moussa B H; Binah, Ofer

    2008-09-01

    We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.

  8. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98.

    Science.gov (United States)

    Loi, Sherene; Sirtaine, Nicolas; Piette, Fanny; Salgado, Roberto; Viale, Giuseppe; Van Eenoo, Françoise; Rouas, Ghizlane; Francis, Prudence; Crown, John P A; Hitre, Erika; de Azambuja, Evandro; Quinaux, Emmanuel; Di Leo, Angelo; Michiels, Stefan; Piccart, Martine J; Sotiriou, Christos

    2013-03-01

    Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case, anthracycline-only CT-in selected BC subtypes. We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years. There was no significant prognostic association in the global nor estrogen receptor (ER) -positive/human epidermal growth factor receptor 2 (HER2) -negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018). In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor

  9. Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors.

    Directory of Open Access Journals (Sweden)

    A B Madhankumar

    Full Text Available Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs. Interleukin-13 receptor alpha 2 (IL13Rα2 is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR. This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.

  10. Separation of mercury(II), methylmercury and phenylmercury by micellar high-performance liquid chromatography on short columns

    International Nuclear Information System (INIS)

    Hutta, M.; Megova, S.; Halko, R.

    1998-01-01

    Three environmentally and agrochemically important mercury species: methylmercury, phenylmercury and mercury(II) are separated within 4 minutes as bromocomplexes by micellar liquid chromatography using very short reversed-phase (RP) C18 columns (up to 30 mm). The micellar mobile phase containing 0.05M cetyltrimethylammonium bromide (CTMA + Br - ), 1% (v/v) 2-propanol, 0.001M cyclohexylenediaminetetraacetic acid (DCTA) and sulfuric acid (pH 2) showed good selectivity in mixed reversed-phase and anion-exchange mode. The above mentioned separation order in which organomercurials are eluted far behind the void volume of the column, but before the mercury(II) peak is advantageous in all instances where mercury(II) is present in real samples in great excess. Environmental and agrochemical samples contain humic material which does not interfere in this particular system. The low cost photometric detection at 500 nm after post-column derivatization by CTMA + Br - micellized dithizone is almost free from interferences and enables detection limits at the 1-3 ng level (e.g., 0.1 ppm Hg) for 20 μl samples. (author)

  11. Radiation decomposition of alcohols and chloro phenols in micellar systems

    International Nuclear Information System (INIS)

    Moreno A, J.

    1998-01-01

    The effect of surfactants on the radiation decomposition yield of alcohols and chloro phenols has been studied with gamma doses of 2, 3, and 5 KGy. These compounds were used as typical pollutants in waste water, and the effect of the water solubility, chemical structure, and the nature of the surfactant, anionic or cationic, was studied. The results show that anionic surfactant like sodium dodecylsulfate (SDS), improve the radiation decomposition yield of ortho-chloro phenol, while cationic surfactant like cetyl trimethylammonium chloride (CTAC), improve the radiation decomposition yield of butyl alcohol. A similar behavior is expected for those alcohols with water solubility close to the studied ones. Surfactant concentrations below critical micellar concentration (CMC), inhibited radiation decomposition for both types of alcohols. However radiation decomposition yield increased when surfactant concentrations were bigger than the CMC. Aromatic alcohols decomposition was more marked than for linear alcohols decomposition. On a mixture of alcohols and chloro phenols in aqueous solution the radiation decomposition yield decreased with increasing surfactant concentration. Nevertheless, there were competitive reactions between the alcohols, surfactants dimers, hydroxyl radical and other reactive species formed on water radiolysis, producing a catalytic positive effect in the decomposition of alcohols. Chemical structure and the number of carbons were not important factors in the radiation decomposition. When an alcohol like ortho-chloro phenol contained an additional chlorine atom, the decomposition of this compound was almost constant. In conclusion the micellar effect depend on both, the nature of the surfactant (anionic or cationic) and the chemical structure of the alcohols. The results of this study are useful for wastewater treatment plants based on the oxidant effect of the hydroxyl radical, like in advanced oxidation processes, or in combined treatment such as

  12. The Oral Bioavailability of Trans-Resveratrol from a Grapevine-Shoot Extract in Healthy Humans is Significantly Increased by Micellar Solubilization.

    Science.gov (United States)

    Calvo-Castro, Laura A; Schiborr, Christina; David, Franziska; Ehrt, Heidi; Voggel, Jenny; Sus, Nadine; Behnam, Dariush; Bosy-Westphal, Anja; Frank, Jan

    2018-05-01

    Grapevine-shoot extract Vineatrol30 contains abundant resveratrol monomers and oligomers with health-promoting potential. However, the oral bioavailability of these compounds in humans is low (˂1-2%). The aim of this study was to improve the oral bioavailability of resveratrol from vineatrol by micellar solubilization. Twelve healthy volunteers (six women, six men) randomly ingested a single dose of 500 mg vineatrol (30 mg trans-resveratrol, 75 mg trans-ε-viniferin) as native powder or liquid micelles. Plasma and urine were collected at baseline and over 24 h after intake. Resveratrol and viniferin were analyzed by HPLC. The area under the plasma concentration-time curve (AUC) and mean maximum plasma trans-resveratrol concentrations were 5.0-fold and 10.6-fold higher, respectively, after micellar supplementation relative to the native powder. However, no detectable amounts of trans-ε-viniferin were found in either plasma or urine. The transepithelial permeability of trans-resveratrol and trans-ε-viniferin across differentiated Caco-2 monolayers was consistent to the absorbed fractions in vivo. The oral bioavailability of trans-resveratrol from the grapevine-shoot extract Vineatrol30 was significantly increased using a liquid micellar formulation, without any treatment-related adverse effects, making it a suitable system for improved supplementation of trans-resveratrol. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Infusion's greenfield subsidiary in Poland

    NARCIS (Netherlands)

    Williams, C.; van Eerde, W.; The, D.

    2012-01-01

    The president of Infusion Development Corporation was reviewing the progress of the new subsidiary the company had set up 15 months earlier in Krakow, Poland. The purpose of the subsidiary was to work with other Infusion offices around the world to provide innovative software development services to

  14. Optimisation of resolution in micellar electrokinetic chromatography by multivariate evaluation of electrolytes.

    Science.gov (United States)

    Mikaeli, S; Thorsén, G; Karlberg, B

    2001-01-12

    A novel approach to multivariate evaluation of separation electrolytes for micellar electrokinetic chromatography is presented. An initial screening of the experimental parameters is performed using a Plackett-Burman design. Significant parameters are further evaluated using full factorial designs. The total resolution of the separation is calculated and used as response. The proposed scheme has been applied to the optimisation of the separation of phenols and the chiral separation of (+)-1-(9-anthryl)-2-propyl chloroformate-derivatized amino acids. A total of eight experimental parameters were evaluated and optimal conditions found in less than 48 experiments.

  15. Doxorubicin-conjugated bacteriophages carrying anti-MHC class I chain-related A for targeted cancer therapy in vitro

    Directory of Open Access Journals (Sweden)

    Phumyen A

    2014-11-01

    Full Text Available Achara Phumyen,1–3 Siriporn Jantasorn,1 Amonrat Jumnainsong,1 Chanvit Leelayuwat1–4 1The Centre for Research and Development of Medical Diagnostic Laboratories (CMDL, Faculty of Associated Medical Sciences, 2The Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, 3Research Cluster: Specific Health Problem of Grater Maekong Subregion (SHeP-GMS, 4Department of Clinical Immunology and Transfusion Sciences, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand Background: Cancer therapy by systemic administration of anticancer drugs, besides the effectiveness shown on cancer cells, demonstrated the side effects and cytotoxicity on normal cells. The targeted drug-carrying nanoparticles may decrease the required drug concentration at the site and the distribution of drugs to normal tissues. Overexpression of major histocompatibility complex class I chain–related A (MICA in cancer is useful as a targeted molecule for the delivery of doxorubicin to MICA-expressing cell lines. Methods: The application of 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide (EDC chemistry was employed to conjugate the major coat protein of bacteriophages carrying anti-MICA and doxorubicin in a mildly acid condition. Doxorubicin (Dox on phages was determined by double fluorescence of phage particles stained by M13-fluorescein isothiocyanate (FITC and drug autofluorescence by flow cytometry. The ability of anti-MICA on phages to bind MICA after doxorubicin conjugation was evaluated by indirect enzyme-linked immunosorbent assay. One cervical cancer and four cholangiocarcinoma cell lines expressing MICA were used as models to evaluate targeting activity by cell cytotoxicity test. Results: Flow cytometry and indirect enzyme-linked immunosorbent assay demonstrated that most of the phages (82% could be conjugated with doxorubicin, and the Dox-carrying phage-displaying anti-MICA (Dox-phage remained the binding activity against MICA

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  17. Micellar phase boundaries under the influence of ethyl alcohol

    International Nuclear Information System (INIS)

    Bergeron, Denis E.

    2016-01-01

    The Compton spectrum quenching technique is used to monitor the effect of ethyl alcohol (EtOH) additions on phase boundaries in two systems. In toluenic solutions of the nonionic surfactant, Triton X-100, EtOH shifts the boundary separating the first clear phase from the first turbid phase to higher water:surfactant ratios. In a commonly used scintillant, Ultima Gold AB, the critical micelle concentration is not shifted. The molecular interactions behind the observations and implications for liquid scintillation counting are discussed. - Highlights: • Compton spectrum quenching technique applied to find micellar phase boundaries. • Toluenic Triton X-100 and Ultima Gold AB investigated. • Ethyl alcohol affects phase boundaries in Triton X-100, not in Ultima Gold AB. • Phase boundary observations discussed in terms of relevant molecular interactions.

  18. Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study.

    Science.gov (United States)

    Amoroso, Loredana; Erminio, Giovanni; Makin, Guy; Pearson, Andrew D J; Brock, Penelope; Valteau-Couanet, Dominique; Castel, Victoria; Pasquet, Marlène; Laureys, Genevieve; Thomas, Caroline; Luksch, Roberto; Ladenstein, Ruth; Haupt, Riccardo; Garaventa, Alberto

    2018-01-01

    Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([ 123 I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m 2 /day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m 2 , and doxorubicin, 45 mg/m 2 . Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

  19. Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin.

    Science.gov (United States)

    Hattori, Yoshiyuki; Shibuya, Kazuhiko; Kojima, Kaori; Miatmoko, Andang; Kawano, Kumi; Ozaki, Kei-Ichi; Yonemochi, Etsuo

    2015-07-01

    Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed. Furthermore, ZOL treatments induced inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α in serum of LLC tumor-bearing mice, but not in normal mice, indicating that ZOL treatments might induce an inflammatory response in tumor tissue. Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing a subcutaneous LLC tumor, although they did not significantly increase the tumor accumulation of doxorubicin (DXR). These results suggest that ZOL treatments might increase the therapeutic efficacy of Doxil via improvement of DXR distribution in a tumor by changing the tumor vasculature. ZOL treatment can be an alternative approach to increase the antitumor effect of liposomal drugs.

  20. Pharmacokinetics and toxicology of continuously infused nitroimidazoles

    International Nuclear Information System (INIS)

    Eifel, P.J.; Brown, J.M.

    1984-01-01

    The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures

  1. MONITORING TETESAN INFUS BERBASIS MIKROKONTROLER ATMEGA16

    Directory of Open Access Journals (Sweden)

    Ardiyanto Iqbal Nugroho

    2015-09-01

    Penelitian ini menghasilkan suatu alat monitoring tetesan infus yang dapat memberikan informasi mengenai laju kecepatan tetesan dan kondisi cairan pada infus. Sistem yang secara realtime dimonitoring oleh perawat ini dapat mengurangi permasalahan yang timbul karena kelalaian petugas. Sehingga perawat tidak secara manual dalam mengatur kecepatan tetesan infus dan meningkatkan pelayanan kepada pasien.

  2. Determination of 24-hour insulin infusion pattern by an artificial endocrine pancreas for intravenous insulin infusion with a miniature pump

    DEFF Research Database (Denmark)

    Kølendorf, K; Christiansen, J S; Bojsen, J

    1981-01-01

    UNLABELLED: Intravenous insulin infusion with a glucose controlled insulin infusion system (GCIIS) is known to restore glucose homeostasis. A simpler approach to improve blood glucose regulation is preprogrammed intravenous insulin infusion with portable pumps without sensor-mediated feedback. We...... report a study designed to evaluate whether the preprogrammed insulin infusion pattern to be used in the miniature insulin infusion pump (MIIP) could be optimized by concomitant employment of the GCIIS for blood glucose control. Six juvenile-onset insulin-dependent diabetics (mean age 31 yrs) were...... studied. Mean blood glucose (MBG) was 6.2 mmol/l +/- 0.5 (SD) during glucose controlled infusion and 5.3 +/- 0.6 during the combined MIIP + GCIIS-day. The insulin requirements calculated from the s.c. regimen (56 U +/- 10 SD) were identical to the GCIIS-measured (51 U +/- 14) and to the amounts delivered...

  3. Modeling localized delivery of Doxorubicin to the brain following focused ultrasound enhanced blood-brain barrier permeability

    International Nuclear Information System (INIS)

    Nhan, Tam; Burgess, Alison; Hynynen, Kullervo; Lilge, Lothar

    2014-01-01

    Doxorubicin (Dox) is a well-established chemotherapeutic agent, however it has limited efficacy in treating brain malignancies due to the presence of the blood-brain barrier (BBB). Recent preclinical studies have demonstrated that focused ultrasound induced BBB disruption (BBBD) enables efficient delivery of Dox to the brain. For future treatment planning of BBBD-based drug delivery, it is crucial to establish a mathematical framework to predict the effect of transient BBB permeability enhancement on the spatiotemporal distribution of Dox at the targeted area. The constructed model considers Dox concentrations within three compartments (plasma, extracellular, intracellular) that are governed by various transport processes (e.g. diffusion in interstitial space, exchange across vessel wall, clearance by cerebral spinal fluid, uptake by brain cells). By examining several clinical treatment aspects (e.g. sonication scheme, permeability enhancement, injection mode), our simulation results support the experimental findings of optimal interval delay between two consecutive sonications and therapeutically-sufficient intracellular concentration with respect to transfer constant K trans range of 0.01–0.03 min −1 . Finally, the model suggests that infusion over a short duration (20–60 min) should be employed along with single-sonication or multiple-sonication at 10 min interval to ensure maximum delivery to the intracellular compartment while attaining minimal cardiotoxicity via suppressing peak plasma concentration. (paper)

  4. Comparison of migration modeling in micellar electrokinetic chromatography by linear regression and by use of an artificial neural network

    NARCIS (Netherlands)

    Metting, HJ; van Zomeren, PV; van der Ley, CP; Coenegracht, PMJ; de Jong, GJ

    2000-01-01

    The concentrations of modifier (methanol or acetonitrile) and surfactant (sodium dodecyl sulfate SDS) in the running buffer are important factors influencing the mobility of analytes in micellar electrokinetic chromatography (MEKC). Response surfaces of the effective mobility can be used to predict

  5. APC loss in breast cancer leads to doxorubicin resistance via STAT3 activation.

    Science.gov (United States)

    VanKlompenberg, Monica K; Leyden, Emily; Arnason, Anne H; Zhang, Jian-Ting; Stefanski, Casey D; Prosperi, Jenifer R

    2017-11-28

    Resistance to chemotherapy is one of the leading causes of death from breast cancer. We recently established that loss of Adenomatous Polyposis Coli (APC) in the Mouse Mammary Tumor Virus - Polyoma middle T (MMTV-PyMT) transgenic mouse model results in resistance to cisplatin or doxorubicin-induced apoptosis. Herein, we aim to establish the mechanism that is responsible for APC-mediated chemotherapeutic resistance. Our data demonstrate that MMTV-PyMT; Apc Min/+ cells have increased signal transducer and activator of transcription 3 (STAT3) activation. STAT3 can be constitutively activated in breast cancer, maintains the tumor initiating cell (TIC) population, and upregulates multidrug resistance protein 1 (MDR1). The activation of STAT3 in the MMTV-PyMT; Apc Min/+ model is independent of interleukin 6 (IL-6); however, enhanced EGFR expression in the MMTV-PyMT; Apc Min/+ cells may be responsible for the increased STAT3 activation. Inhibiting STAT3 with a small molecule inhibitor A69 in combination with doxorubicin, but not cisplatin, restores drug sensitivity. A69 also decreases doxorubicin enhanced MDR1 gene expression and the TIC population enhanced by loss of APC. In summary, these results have revealed the molecular mechanisms of APC loss in breast cancer that can guide future treatment plans to counteract chemotherapeutic resistance.

  6. Correlation between the solubility of aromatic hydrocarbons in water and micellar solutions, with their normal boiling points

    International Nuclear Information System (INIS)

    Almgren, M.; Grieser, F.; Powell, J.R.; Thomas, J.K.

    1979-01-01

    A linear correlation between the logarithm of the solubility in water of aromatic hydrocarbons and their normal boiling points is shown. Similarly, the logarithm of the distribution ratio of aromatic hydrocarbons in aqueous micellar solution is shown to be linearly related to the boiling points of the hydrocarbons. 2 figures, 2 tables

  7. Infusing PDA technology into nursing education.

    Science.gov (United States)

    White, Ann; Allen, Patricia; Goodwin, Linda; Breckinridge, Daya; Dowell, Jeffery; Garvy, Ryan

    2005-01-01

    Use of the personal digital assistant (PDA) has been infused into the accelerated baccalaureate program at Duke University to help prepare nursing students for professional practice. The authors provide an overview of the use of PDAs in the classroom, laboratory, and clinical setting. Technical aspects of PDA infusion and steps to ensure regulatory compliance are explored. Benefits of PDA use by both faculty and students in the program and challenges met with the infusion of this technology are also described.

  8. Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Y. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Shen, H. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Cao, Y. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Li, H. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Qin, R. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Chen, Q. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Long, L. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Zhu, X.L. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Xie, C.J. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Xu, W.L. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China)

    2014-01-10

    MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.

  9. Xanthohumol, a Prenylated Chalcone from Hops, Inhibits the Viability and Stemness of Doxorubicin-Resistant MCF-7/ADR Cells

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2016-12-01

    Full Text Available Xanthohumol is a unique prenylated flavonoid in hops (Humulus lupulus L. and beer. Xanthohumol has been shown to possess a variety of pharmacological activities. There is little research on its effect on doxorubicin-resistant breast cancer cells (MCF-7/ADR and the cancer stem-like cells exiting in this cell line. In the present study, we investigate the effect of xanthohumol on the viability and stemness of MCF-7/ADR cells. Xanthohumol inhibits viability, induces apoptosis, and arrests the cell cycle of MCF-7/ADR cells in a dose-dependent manner; in addition, xanthohumol sensitizes the inhibition effect of doxorubicin on MCF-7/ADR cells. Interestingly, we also find that xanthohumol can reduce the stemness of MCF-7/ADR cells evidenced by the xanthohumol-induced decrease in the colony formation, the migration, the percentage of side population cells, the sphere formation, and the down-regulation of stemness-related biomarkers. These results demonstrate that xanthohumol is a promising compound targeting the doxorubicin resistant breast cancer cells and regulating their stemness, which, therefore, will be applied as a potential candidate for the development of a doxorubicin-resistant breast cancer agent and combination therapy of breast cancer.

  10. Potentiation of in vitro and in vivo antitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Rathos, Maggie J; Khanwalkar, Harshal; Joshi, Kavita; Manohar, Sonal M; Joshi, Kalpana S

    2013-01-01

    In the present study, we show that the combination of doxorubicin with the cyclin-dependent kinase inhibitor P276-00 was synergistic at suboptimal doses in the non-small cell lung carcinoma (NSCLC) cell lines and induces extensive apoptosis than either drug alone in H-460 human NSCLC cells. Synergistic effects of P276-00 and doxorubicin on growth inhibition was studied using the Propidium Iodide (PI) assay. The doses showing the best synergistic effect was determined and these doses were used for further mechanistic studies such as western blotting, cell cycle analysis and RT-PCR. The in vivo efficacy of the combination was evaluated using the H-460 xenograft model. The combination of 100 nM doxorubicin followed by 1200 nM P276-00 showed synergistic effect in the p53-positive and p53-mutated cell lines H-460 and H23 respectively as compared to the p53-null cell line H1299. Abrogation of doxorubicin-induced G2/M arrest and induction of apoptosis was observed in the combination treatment. This was associated with induction of tumor suppressor protein p53 and reduction of anti-apoptotic protein Bcl-2. Furthermore, doxorubicin alone greatly induced COX-2, a NF-κB target and Cdk-1, a target of P276-00, which was downregulated by P276-00 in the combination. Doxorubicin when combined with P276-00 in a sequence-specific manner significantly inhibited tumor growth, compared with either doxorubicin or P276-00 alone in H-460 xenograft model. These findings suggest that this combination may increase the therapeutic index over doxorubicin alone and reduce systemic toxicity of doxorubicin most likely via an inhibition of doxorubicin-induced chemoresistance involving NF-κB signaling and inhibition of Cdk-1 which is involved in cell cycle progression

  11. Chemoembolization (TACE) of Unresectable Intrahepatic Cholangiocarcinoma with Slow-Release Doxorubicin-Eluting Beads: Preliminary Results

    International Nuclear Information System (INIS)

    Aliberti, Camillo; Benea, Giorgio; Tilli, Massimo; Fiorentini, Giammaria

    2008-01-01

    The purpose of this study was to evaluate the safety and efficacy of TACE with microspheres preloaded with doxorubicin in unresectable intrahepatic cholangiocarcinoma (UCH). Twenty patients with UCH were observed; 9 refused, preferring other palliative care or chemotherapy, and 11 agreed to be treated with one or more cycles of DC beads loaded with doxorubicin (100-150 mg) in a TACE procedure between February 2006 and September 2007. A total of 29 individual TACE procedures were performed. Follow-up imaging was performed on all patients before, immediately after, and 4 weeks after each TACE procedure to evaluate the response and need for further treatment. Each patient received i.v hydration, antibiotics, and medications against nausea and pain before TACE. Survival rate was calculated using Kaplan-Meier survival curve. A response rate of 100% followed RECIST criteria was observed. Eight of eleven patients are alive, with a median survival of 13 months. TACE was well tolerated by all patients. One patient developed hepatic abscess requiring antibiotic therapy. No evidence of marrow toxicity has been reported. Only one of nine patients treated with chemotherapy or palliative care is alive (with a median survival of 7 months in this group of patients). In conclusion, we suggest that doxorubicin-eluting beads TACE is a feasible and effective treatment in patients with UCH. Survival seems to be clearly prolonged in the treated group with respect to the palliative group. We consider that doxorubicin-eluting beads TACE of 100-150 mg may be an appropriate palliative therapy for these patients. Further studies are warranted to confirm these interesting preliminary data.

  12. The effect of glucagon on infusion cholangiography

    International Nuclear Information System (INIS)

    Evans, A.F.; Whitehouse, G.H.

    1979-01-01

    An assessment has been made of the effects of glucagon on biliary tract opacification during intravenous cholangiography. Two series of infusion cholangiograms were obtained at two investigating centres designated A and B. In series A, 41 patients had ioglycamide infusions at a rate of 0.2833 g min -1 over 1 h. In series B, 31 patients had ioglycamide infusions at a rate of 0.3886 g min -1 over 30 min. Radiographs were taken in both series immediately at the end of the infusion, 10 min later and 30 min after the infusion. Two mg of intravenous glucagon was injected into alternate cases in both series A and B immediately after the first radiograph was taken at the completion of the ioglycamide infusion. Two observers in each series then assessed the radiographic opacification of the biliary system without prior knowledge of which patients had received the glucagon. Delineation of the biliary system was considered better in both series in those patients who received glucagon when compared with the controls. Gallbladder opacification was definitely increased in series A in those receiving glucagon, and a similar tendency was shown in series B. The amount of contrast in the upper intestine was increased in series A in the glucagon group, but not in series B. It is concluded that glucagon improves visualisation of the biliary tract, especially the gallbladder at infusion cholangiography. (author)

  13. Pulsatile versus steady infusions for hepatic artery chemotherapy

    International Nuclear Information System (INIS)

    Kim, E.E.; Haynie, T.P.; Wright, K.C.; Chaynsangavej, C.; Gianturco, C.; Lamki, L.; Wallace, S.

    1984-01-01

    Hepatic artery chemotherapy for unresectable liver tumors requires an even distribution of the drugs in the tumor or vascular bed. This cannot be determined angiographically because the drugs are infused at a much lower rate than the contrast media. It is easy, however, to determine the quality of the perfusion by injecting a small volume of Tc-99m MAA in one of the side ports while chemotherapeutic agent is being infused at the same rate. Usually this shows a uniform, satisfactory distribution of isotope. Occasionally, however, some areas fail to receive Tc-99m in spite of what appears to be a good position of the catheter tip. Since ''streaming'' of the infused drugs has been blamed for their uneven distribution, the authors decided to compare the usual steady flow infusions with infusions made pulsatile by the addition of a pulsing device (Gianturco Pump) attached to the infusion tubing. Eighty-three patients were studied with steady as well as pulsatile infusions. In 16 of these patients the perfusion pattern was definitely changed by the pulsatile infusion. In one patient the pulsatile mode resulted in an unwanted gastric perfusion. In 5 patients the distribution was improved in one hepatic lobe and in 10 patients it was improved in both lobes. These results show that hepatic artery perfusions can occasionally be improved by pulsing the infusate. However, pulsing can produce the unwanted perfusion of extra-hepatic areas

  14. In situ synthesis of Prussian blue nanoparticles within a biocompatible reverse micellar system for in vivo Cs"+ uptake

    International Nuclear Information System (INIS)

    Lavaud, Cyril; Kajdan, Marilyn; Long, Jerome; Larionova, Joulia; Guari, Yannick; Compte, Elsa; Maurel, Jean-Claude; Him, Josephine Lai Kee; Bron, Patrick; Oliviero, Erwan

    2017-01-01

    A new highly stable Prussian blue reverse micellar system comprising ultra-small Prussian blue nanoparticles in Aonyss (Peceolt, b-sitosterol, lecithin, ethanol and water) acts as an in vivo Cs"+ uptake agent presenting higher efficiency compared to commercially available Prussian blue treatment with a significant dose effect. (authors)

  15. Doxorubicin plus paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Dombernowsky, P; Boesgaard, M; Andersen, E

    1997-01-01

    . As of February 1997, 34 patients have been enrolled, two patients are too early to evaluate, and 13 are continuing treatment. The preliminary response rate is 69% (95% confidence interval, 50% to 84%), ranging from 60% to 80% within the three schedules. The main toxicities consisted of grade 3/4 neutropenia...... in 65% of all courses, with febrile neutropenia in 2%. Stomatitis and paresthesia were rare. To date, eight of 32 patients have developed abnormal left ventricular ejection fraction values and one patient has developed congestive heart failure. Our preliminary conclusions are that bolus doxorubicin...

  16. Liquid-liquid displacement in slippery liquid-infused membranes (SLIMs)

    OpenAIRE

    Bazyar, Hanieh; Lv, Pengyu; Wood, Jeffery A.; Porada, Slawomir; Lohse, Detlef; Lammertink, Rob G. H.

    2018-01-01

    Liquid-infused membranes inspired by slippery liquid-infused porous surfaces (SLIPS) have been recently introduced to membrane technology. The gating mechanism of these membranes is expected to give rise to anti-fouling properties and multi-phase transport capabilities. However, the long-term retention of the infusion liquid has not yet been explored. To address this issue, we investigate the retention of the infusion liquid in slippery liquid-infused membranes (SLIMs) via liquid-liquid displ...

  17. Synergistic Cytotoxicity Effect by Combination Treatment of Polyketide Derivatives from Annona muricata Linn Leaves and Doxorubicin as Potential Anticancer Material on Raji Cell Line

    Science.gov (United States)

    Artanti, A. N.; Astirin, O. P.; Prayito, A.; Fisma, R.; Prihapsara, F.

    2018-03-01

    Nasopharynx cancer is one of the most deadly cancer. The main priority of nasopharynx cancer treatment is the use of chemotherapeutic agents, especially doxorubicin. However, doxorubicin might also lead to diverse side effect. An approach recently develop to overcome side effect of doxorubicin is to used of combined chemotherapeutic agent. One of the compounds found effication as an anticancer agent on nasopharynx cancer is acetogenin, a polyketide compound that is abundant in Annona muricata L. leaves. This study has been done to examine polyketide derivatives was isolated from Annona muricata L. which has potency to induce apoptosis by p53 expression on raji cell line. The determination of cytotoxic combination activity from polyketide derivative and doxorubicin was evaluated using MTT assay to obtain the value of CI (combination index). Data analysis showed that combination of polyketide derivative from Annona muricata L. (14,4 µg/ml) and doxorubicin with all of concentration performed synergistic effect on raji cell line with CI value from 0.13 – 0.65.

  18. Ring opening metathesis polymerization-derived block copolymers bearing chelating ligands: synthesis, metal immobilization and use in hydroformylation under micellar conditions

    Directory of Open Access Journals (Sweden)

    Gajanan M. Pawar

    2010-03-01

    Full Text Available Norborn-5-ene-(N,N-dipyrid-2-ylcarbamide (M1 was copolymerized with exo,exo-[2-(3-ethoxycarbonyl-7-oxabicyclo[2.2.1]hept-5-en-2-carbonyloxyethyl]trimethylammonium iodide (M2 using the Schrock catalyst Mo(N-2,6-Me2-C6H3(CHCMe2Ph(OCMe(CF322 [Mo] to yield poly(M1-b-M2. In water, poly(M1-b-M2 forms micelles with a critical micelle-forming concentration (cmc of 2.8 × 10−6 mol L−1; Reaction of poly(M1-b-M2 with [Rh(CODCl]2 (COD = cycloocta-1,5-diene yields the Rh(I-loaded block copolymer poly(M1-b-M2-Rh containing 18 mg of Rh(I/g of block copolymer with a cmc of 2.2 × 10−6 mol L−1. The Rh-loaded polymer was used for the hydroformylation of 1-octene under micellar conditions. The data obtained were compared to those obtained with a monomeric analogue, i.e. CH3CON(Py2RhCl(COD (C1, Py = 2-pyridyl. Using the polymer-supported catalyst under micellar conditions, a significant increase in selectivity, i.e. an increase in the n:iso ratio was accomplished, which could be further enhanced by the addition of excess ligand, e.g., triphenylphosphite. Special features of the micellar catalytic set up are discussed.

  19. Micellar effect on the kinetics of oxidation of methyl blue by Ce(IV in sulfuric acid medium

    Directory of Open Access Journals (Sweden)

    Mohammed Hassan

    2015-01-01

    Full Text Available The kinetics of oxidation of methyl blue (MB by Ce(IV in aqueous and surfactant media has been carried out to explore the micellar effect on the rate and kinetic parameters of the reaction. The reaction was found to be first order with respect to both oxidant and substrate and fractional order with respect to H+. The active kinetic species of the oxidant was found to be Ce(SO4+2 based on the effect of ionic strength and sulfate ion on the rate of the reaction. The presence of micelles was found to inhibit the reaction and this effect has been explained by the association of one of the reactants with the micelles leaving the other reactant in the bulk solution. The binding constant and first order rate constant in micellar medium has been obtained by the application of pseudo-phase model to the experimental data. Interestingly, the temperature dependence of the reaction reveals that the reaction has negative activation energy in the absence of micelles, which turns to a positive value in the presence of micelles.

  20. Application of micellar electrokinetic capillary chromatography for routine analysis of different materials

    Directory of Open Access Journals (Sweden)

    Injac Rade

    2008-01-01

    Full Text Available Micellar electrokinetic capillary chromatography (MEKC has become a popular mode among the several capillary electro-migration techniques. Most drug analysis can be performed by using MEKC because of its wide applicability. Separation of very complex mixtures, determination of drugs in the biological materials, etc., can be successfully achieved by MEKC. This review surveys typical applications of MEKC analysis. Recent advances in MEKC, especially with solid-phase extraction and large-volume sample stacking, are described. Modes of electrokinetic chromatography including MEKC, a separation theory of MEKC, environmental friendly analysis, and selectivity manipulation in MEKC are also briefly mentioned.

  1. Financial analysis for the infusion alliance.

    Science.gov (United States)

    Perucca, Roxanne

    2010-01-01

    Providing high-quality, cost-efficient care is a major strategic initiative of every health care organization. Today's health care environment is transparent; very competitive; and focused upon providing exceptional service, safety, and quality. Establishing an infusion alliance facilitates the achievement of organizational strategic initiatives, that is, increases patient throughput, decreases length of stay, prevents the occurrence of infusion-related complications, enhances customer satisfaction, and provides greater cost-efficiency. This article will discuss how to develop a financial analysis that promotes value and enhances the financial outcomes of an infusion alliance.

  2. Influence of micellar calcium and phosphorus on rennet coagulation properties of cows milk.

    Science.gov (United States)

    Malacarne, Massimo; Franceschi, Piero; Formaggioni, Paolo; Sandri, Sandro; Mariani, Primo; Summer, Andrea

    2014-05-01

    The main requirement for milk processed in most cheese typologies is its rennet coagulation ability. Despite the increasing number of studies, the causes for abnormal coagulation of milk are not fully understood. The aim of this study was to ascertain relationships between milk characteristics and its rennet coagulation ability, focusing on the influence of calcium (Ca) and phosphorus (P). Ca and P are essential constituents of the micelles. Micellar P can be present as part of colloidal calcium phosphate (inorganic-P) or covalently bound to caseins as phosphate groups (casein-P). Eighty one herd milk samples (SCCproperties. Optimal milk was characterised by the highest contents of major constituents, protein fractions and minerals, lowest content of chloride and highest values of titratable acidity. Non-coagulating milk was characterised by the highest values of pH and the lowest of titratable acidity. At micellar level, Optimal milk showed the highest values of colloidal Ca, casein-P and colloidal Mg (g/100 g casein), while Non-coagulating milk showed the lowest values. Interestingly, there was no statistical difference regarding the content of colloidal inorganic-P (g/100 g casein) between Optimal and Non-coagulating milks. Overall, high mineralisation of the micelle (expressed as g inorganic-P/100 g casein) positively affect its rennetability. However, excessive mineralisation could lead to a reduction of the phosphate groups (g casein-P/100 g casein) available for curd formation.

  3. Determination of lysergic acid diethylamide (LSD) in mouse blood by capillary electrophoresis/ fluorescence spectroscopy with sweeping techniques in micellar electrokinetic chromatography.

    Science.gov (United States)

    Fang, Ching; Liu, Ju-Tsung; Chou, Shiu-Huey; Lin, Cheng-Huang

    2003-03-01

    The separation and on-line concentration of lysergic acid diethylamide (LSD) in mouse blood was achieved by means of capillary electrophoresis/fluorescence spectroscopy using sodium dodecyl sulfate (SDS) as the surfactant. Techniques involving on-line sample concentration, including sweeping micellar electrokinetic chromatography (sweeping-MEKC) and cation-selective exhaustive injection-sweep-micellar electrokinetic chromatography (CSEI-sweep-MEKC) were applied; the optimum on-line concentration and separation conditions were determined. In the analysis of an actual sample, LSD was found in a blood sample from a test mouse (0.1 mg LSD fed to a 20 g mouse; approximately 1/10 to the value of LD(50)). As a result, 120 and 30 ng/mL of LSD was detected at 20 and 60 min, respectively, after ingestion of the doses.

  4. Efficacy, safety and anticancer activity of protein nanoparticle-based delivery of doxorubicin through intravenous administration in rats.

    Directory of Open Access Journals (Sweden)

    Kishore Golla

    Full Text Available Doxorubicin is a potent anticancer drug and a major limiting factor that hinders therapeutic use as its high levels of systemic circulation often associated with various off-target effects, particularly cardiotoxicity. The present study focuses on evaluation of the efficacy of doxorubicin when it is loaded into the protein nanoparticles and delivered intravenously in rats bearing Hepatocellular carcinoma (HCC. The proteins selected as carrier were Apotransferrin and Lactoferrin, since the receptors for these two proteins are known to be over expressed on cancer cells due to their iron transport capacity.Doxorubicin loaded apotransferrin (Apodoxonano and lactoferrin nanoparticles (Lactodoxonano were prepared by sol-oil chemistry. HCC in the rats was induced by 100 mg/l of diethylnitrosamine (DENA in drinking water for 8 weeks. Rats received 5 doses of 2 mg/kg drug equivalent nanoparticles through intravenous administration. Pharmacokinetics and toxicity of nanoformulations was evaluated in healthy rats and anticancer activity was studied in DENA treated rats. The anticancer activity was evaluated through counting of the liver nodules, H & E analysis and by estimating the expression levels of angiogenic and antitumor markers.In rats treated with nanoformulations, the numbers of liver nodules were found to be significantly reduced. They showed highest drug accumulation in liver (22.4 and 19.5 µg/g. Both nanoformulations showed higher localization compared to doxorubicin (Doxo when delivered in the absence of a carrier. Higher amounts of Doxo (195 µg/g were removed through kidney, while Apodoxonano and Lactodoxonano showed only a minimal amount of removal (<40 µg/g, suggesting the extended bioavailability of Doxo when delivered through nanoformulation. Safety analysis shows minimal cardiotoxicity due to lower drug accumulation in heart in the case of nanoformulation.Drug delivery through nanoformulations not only minimizes the cardiotoxicity of

  5. AMP-activated protein kinase α2 and E2F1 transcription factor mediate doxorubicin-induced cytotoxicity by forming a positive signal loop in mouse embryonic fibroblasts and non-carcinoma cells.

    Science.gov (United States)

    Yang, Wookyeom; Park, In-Ja; Yun, Hee; Im, Dong-Uk; Ock, Sangmi; Kim, Jaetaek; Seo, Seon-Mi; Shin, Ha-Yeon; Viollet, Benoit; Kang, Insug; Choe, Wonchae; Kim, Sung-Soo; Ha, Joohun

    2014-02-21

    Doxorubicin is one of the most widely used anti-cancer drugs, but its clinical application is compromised by severe adverse effects in different organs including cardiotoxicity. In the present study we explored mechanisms of doxorubicin-induced cytotoxicity by revealing a novel role for the AMP-activated protein kinase α2 (AMPKα2) in mouse embryonic fibroblasts (MEFs). Doxorubicin robustly induced the expression of AMPKα2 in MEFs but slightly reduced AMPKα1 expression. Our data support the previous notion that AMPKα1 harbors survival properties under doxorubicin treatment. In contrast, analyses of Ampkα2(-/-) MEFs, gene knockdown of AMPKα2 by shRNA, and inhibition of AMPKα2 activity with an AMPK inhibitor indicated that AMPKα2 functions as a pro-apoptotic molecule under doxorubicin treatment. Doxorubicin induced AMPKα2 at the transcription level via E2F1, a transcription factor that regulates apoptosis in response to DNA damage. E2F1 directly transactivated the Ampkα2 gene promoter. In turn, AMPKα2 significantly contributed to stabilization and activation of E2F1 by doxorubicin, forming a positive signal amplification loop. AMPKα2 directly interacted with and phosphorylated E2F1. This signal loop was also detected in H9c2, C2C12, and ECV (human epithelial cells) cells as well as mouse liver under doxorubicin treatment. Resveratrol, which has been suggested to attenuate doxorubicin-induced cytotoxicity, significantly blocked induction of AMPKα2 and E2F1 by doxorubicin, leading to protection of these cells. This signal loop appears to be non-carcinoma-specific because AMPKα2 was not induced by doxorubicin in five different tested cancer cell lines. These results suggest that AMPKα2 may serve as a novel target for alleviating the cytotoxicity of doxorubicin.

  6. Activity of trypsin-like enzymes and gelatinases in rats with doxorubicin cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Iu. А. Gordiienko

    2014-12-01

    Full Text Available Activity of trypsin-like enzymes (ATLE and gelatinases A and B were studied in the blood plasma and extracts from cardiac muscle, cerebral cortex and cerebellum of rats with cardiomyopathy caused by anthracycline antibiotic doxorubicin against the background of preventive application of corvitin and α-ketoglutarate. ATLE significantly increased in blood plasma and extracts from cerebral cortex but decreased in extracts from cardiac muscle and cerebellum in doxorubicin cardiomyopathy (DCMP. In addition, a significant increase of activity of both gelatinases in plasma and tissue extracts was observed. Preventive administration of corvitin and α-ketoglutarate resulted in differently directed changes of activity of the above mentioned enzymes in heart and brain tissues. Obtained data confirm the hypothesis about activation of proteolysis under the influence of anthracycline antibiotics and testify to selective effect of corvitin and α-ketoglutarate on ATLE and gelatinases.

  7. Activity of trypsin-like enzymes and gelatinases in rats with doxorubicin cardiomyopathy.

    Science.gov (United States)

    Gordiienko, Iu A; Babets, Ya V; Kulinich, A O; Shevtsova, A I; Ushakova, G O

    2014-01-01

    Activity of trypsin-like enzymes (ATLE) and gelatinases A and B were studied in the blood plasma and extracts from cardiac muscle, cerebral cortex and cerebellum of rats with cardiomyopathy caused by anthracycline antibiotic doxorubicin against the background of preventive application of corvitin and α-ketoglutarate. ATLE significantly increased in blood plasma and extracts from cerebral cortex but decreased in extracts from cardiac muscle and cerebellum in doxorubicin cardiomyopathy (DCMP). In addition, a significant increase of activity of both gelatinases in plasma and tissue extracts was observed. Preventive administration of corvitin and α-ketoglutarate resulted in differently directed changes of activity of the above mentioned enzymes in heart and brain tissues. Obtained data confirm the hypothesis about activation of proteolysis under the influence of anthracycline antibiotics and testify to selective effect of corvitin and α-ketoglutarate on ATLE and gelatinases.

  8. Pt/glassy carbon model catalysts prepared from PS-b-P2VP micellar templates.

    Science.gov (United States)

    Gu, Yunlong; St-Pierre, Jean; Ploehn, Harry J

    2008-11-04

    Poly(styrene)-block-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymer was used as a micellar template to fabricate arrays of Pt nanoparticles on mica and glassy carbon (GC) supports. Polymer micellar deposition yields Pt nanoparticles with tunable particle size and surface number density on both mica and GC. After deposition of precursor-loaded micelles onto GC, oxygen plasma etching removes the polymer shell, followed by thermal treatment with H2 gas to reduce the Pt. Etching conditions were optimized to maximize removal of the polymer while minimizing damage to the GC. Arrays of Pt nanoparticles with controlled size and surface number density can be prepared on mica (for particle size characterization) and GC to make Pt/GC model catalysts. These model catalysts were characterized by tapping mode atomic force microscopy, X-ray photoelectron spectroscopy, and cyclic voltammetry to measure activity for oxidation of carbon monoxide or methanol. Cyclic voltammetry results demonstrate the existence of a correlation between Pt particle size and electrocatalytic properties including onset potential, tolerance of carbonaceous adsorbates, and intrinsic activity (based on active Pt area from CO stripping voltammetry). Results obtained with Pt/GC model catalysts duplicate prior results obtained with Pt/porous carbon catalysts therefore validating the synthesis approach and offering a new, tunable platform to study catalyst structure and other effects such as aging on proton exchange membrane fuel cell (PEMFC) reactions.

  9. Pharmacokinetics and efficacy of PEGylated liposomal doxorubicin in an intracranial model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Carey K Anders

    Full Text Available Breast cancer brain metastases (BCBM are a challenging consequence of advanced BC. Nanoparticle agents, including liposomes, have shown enhanced delivery to solid tumors and brain. We compared pharmacokinetics (PK and efficacy of PEGylated liposomal doxorubicin (PLD with non-liposomal doxorubicin (NonL-doxo in an intracranial model of BC.Athymic mice were inoculated intracerebrally with MDA-MB-231-BR-luciferase-expressing cells. Tumor-bearing mice were administered PLD or NonL-doxo at 6 mg/kg IV × 1 and were euthanized prior to and 0.083, 1, 3, 6, 24, 72 and 96 h post-treatment. Samples were processed to measure sum total doxorubicin via HPLC. PLD and NonL-doxo were administered IV weekly as single agents (6 mg/kg or in combination (4.5 mg/kg with the PARP inhibitor, ABT-888, PO 25 mg/kg/day. Efficacy was assessed by survival and bioluminescence.Treatment with PLD resulted in approximately 1,500-fold higher plasma and 20-fold higher intracranial tumor sum total doxorubicin AUC compared with NonL-doxo. PLD was detected at 96 h; NonL-doxo was undetectable after 24 h in plasma and tumor. Median survival of PLD-treated animals was 32 days (d, [CI] 31-38, which was significantly longer than controls (26d [CI 25-28]; p = 0.0012 or NonL-doxo treatment (23.5d [CI 18-28], p = 0.0002. Combination treatment with PLD/ABT-888 yielded improved survival compared to NonL-doxo/ABT-888 (35d [CI 31-38] versus 29.5d [CI 25-34]; p = 0.006.PLD provides both PK and efficacy advantage over NonL-doxo in the treatment of an in vivo model of BCBM. The results provide preclinical rationale to translate findings into early phase trials of PLD, with or without ABT-888, for patients with BCBM.

  10. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021)

    DEFF Research Database (Denmark)

    Tap, William D; Papai, Zsuzsanna; Van Tine, Brian A

    2017-01-01

    group were followed up expectantly whereas patients with stable or responsive disease in the combination group were allowed to continue with evofosfamide monotherapy until documented disease progression. A web-based central randomisation with block sizes of two and four was stratified by extent...... of disease, doxorubicin administration method, and previous systemic therapy. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival, analysed in the intention-to-treat population. Safety analyses were done in all patients who received any amount...

  11. Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro.

    Science.gov (United States)

    Sanna, K; Rofstad, E K

    1994-07-15

    Rodent cell lines can develop resistance to doxorubicin and methotrexate during hypoxic stress. This has so far not been observed in human tumor cell lines. The purpose of our communication is to show that doxorubicin and methotrexate resistance can also develop in human melanoma cells during exposure to hypoxia. Four cell lines (BEX-c, COX-c, SAX-c, WIX-c) have been studied. Cells were exposed to hypoxia (O2 concentration WIX-c. BEX-c and SAX-c were sensitive to methotrexate without hypoxia pre-treatment, whereas COX-c and WIX-c were resistant initially. Hypoxia-induced drug resistance was present immediately after reoxygenation and tended to decrease with time but remained statistically significant even 42 hr after reoxygenation.

  12. Micellar effect on metal-ligand complexes of Co(II, Ni(II, Cu(II and Zn(II with citric acid

    Directory of Open Access Journals (Sweden)

    Nageswara Rao Gollapalli

    2009-12-01

    Full Text Available Chemical speciation of citric acid complexes of Co(II, Ni(II, Cu(II and Zn(II was investigated pH-metrically in 0.0-2.5% anionic, cationic and neutral micellar media. The primary alkalimetric data were pruned with SCPHD program. The existence of different binary species was established from modeling studies using the computer program MINIQUAD75. Alkalimetric titrations were carried out in different relative concentrations (M:L:X = 1:2:5, 1:3:5, 1:5:3 of metal (M to citric acid. The selection of best chemical models was based on statistical parameters and residual analysis. The species detected were MLH, ML2, ML2H and ML2H2. The trend in variation of stability constants with change in mole fraction of the medium is explained on the basis of electrostatic and non-electrostatic forces. Distributions of the species with pH at different compositions of micellar media are also presented.

  13. Infusion Antihypoxants in Children with Critical Conditions

    Directory of Open Access Journals (Sweden)

    Yu. S. Aleksandrovich

    2014-01-01

    Full Text Available Hypoxia and mitochondrial damage are a key component of the pathogenesis and tanatogenesis of a critical condition, suggesting the need for its prevention and maximally rapid elimination. Objective: to analyze the efficacy and safety of infusion antihypoxants used in critically ill children from the results of researches. Materials and methods. Available investigations dealing with infusion therapy in children and papers on the use of infusion antihypoxants in adults in 2005 to 2013 were sought in the medical databases PubMed and Cochrane Library with their free availability and analyzed. Results. The analysis included 70 trials. The pathophysiology and pathobiochemistry of hypoxia in critically ill children are given; the current principles of its correction by infusion therapy are considered in detail. Particular emphasis is placed on trials evaluating the efficacy and safety of succinic acid solutions in children. Main indications for and contraindications to their use are demonstrated. Conclusion. The use of Krebs cycle substrate-based infusion antihypoxants (malate, succinate is an effective and promising procedure for the intensive therapy and correction of hypoxia in both adults and children with critical conditions. Considering the fact that papers on the use of infusion antihypoxants in children are scanty, there is a need for further investigations. 

  14. Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data.

    Science.gov (United States)

    Holmgren, Gustav; Sartipy, Peter; Andersson, Christian X; Lindahl, Anders; Synnergren, Jane

    2018-05-01

    Anthracyclines, such as doxorubicin, are highly efficient chemotherapeutic agents against a variety of cancers. However, anthracyclines are also among the most cardiotoxic therapeutic drugs presently on the market. Chemotherapeutic-induced cardiomyopathy is one of the leading causes of disease and mortality in cancer survivors. The exact mechanisms responsible for doxorubicin-induced cardiomyopathy are not completely known, but the fact that the cardiotoxicity is dose-dependent and that there is a variation in time-to-onset of toxicity, and gender- and age differences suggests that several mechanisms may be involved. In this study, we investigated doxorubicin-induced cardiotoxicity in human pluripotent stem cell-derived cardiomyocytes using proteomics. In addition, different sources of omics data (protein, mRNA, and microRNA) from the same experimental setup were further combined and analyzed using newly developed methods to identify differential expression in data of various origin and types. Subsequently, the results were integrated in order to generate a combined visualization of the findings. In our experimental model system, we exposed cardiomyocytes derived from human pluripotent stem cells to doxorubicin for up to 2 days, followed by a wash-out period of additionally 12 days. Besides an effect on the cell morphology and cardiomyocyte functionality, the data show a strong effect of doxorubicin on all molecular levels investigated. Differential expression patterns that show a linkage between the proteome, transcriptome, and the regulatory microRNA network, were identified. These findings help to increase the understanding of the mechanisms behind anthracycline-induced cardiotoxicity and suggest putative biomarkers for this condition.

  15. Inhibition of doxorubicin-induced senescence by PPARδ activation agonists in cardiac muscle cells: cooperation between PPARδ and Bcl6.

    Directory of Open Access Journals (Sweden)

    Paola Altieri

    Full Text Available Senescence and apoptosis are two distinct cellular programs that are activated in response to a variety of stresses. Low or high doses of the same stressor, i.e., the anticancer drug doxorubicin, may either induce apoptosis or senescence, respectively, in cardiac muscle cells. We have demonstrated that PPARδ, a ligand-activated transcriptional factor that controls lipid metabolism, insulin sensitivity and inflammation, is also involved in the doxorubicin-induced senescence program. This occurs through its interference with the transcriptional repressor protein B cell lymphoma-6 (Bcl6. Low doses of doxorubicin increase the expression of PPARδ that sequesters Bcl6, thus preventing it from exerting its anti-senescent effects. We also found that L-165041, a specific PPARδ activator, is highly effective in protecting cardiomyocytes from doxorubicin-induced senescence through a Bcl6 related mechanism. In fact, L-165041 increases Bcl6 expression via p38, JNK and Akt activation, and at the same time it induces the release of Bcl6 from PPARδ, thereby enabling Bcl6 to bind to its target genes. L-165041 also prevented apoptosis induced by higher doses of doxorubicin. However, while experiments performed with siRNA analysis techniques very clearly showed the weight of Bcl6 in the cellular senescence program, no role was found for Bcl6 in the anti-apoptotic effects of L-165041, thus confirming that senescence and apoptosis are two very distinct stress response cellular programs. This study increases our understanding of the molecular mechanism of anthracycline cardiotoxicity and suggests a potential role for PPARδ agonists as cardioprotective agents.

  16. Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation.

    Science.gov (United States)

    Fatemi, Ahmad; Kazemi, Ahmad; Kashiri, Meysam; Safa, Majid

    2015-01-01

    Recognition of the molecular mechanisms of cAMP action against DNA damage-induced apoptosis can be useful to improve the efficacy of DNA damaging therapeutic agents. Considering the critical role of bcl-2-associated death promoter (BAD) and p53 proteins in DNA damage -induced apoptosis, the aim of this study was to assess the effect of cAMP-elevating agents on these proteins in doxorubicin-treated pre-B acute lymphoblastic leukemia (pre-B ALL) NALM-6 cells.The pre-B ALL cell line NALM-6 was cultured and treated with doxorubicin in combination with or without cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX). Cell viability was measured by trypan blue staining and MTT assay. For evaluation of apoptosis, annexin-V staining by flow cytometry and caspase-3 activity assay were used. Protein expression of p53, BAD and phoshorylated BAD was detected by western blotting analysis.cAMP-increasing agents diminished the doxorubicin-mediated cytotoxicity in NALM-6 cells as indicated by the viability assays. Annexin-V apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis. Moreover, doxorubicin-induced caspase-3 activity was attenuated in the presence of cAMP-increasing agents. Western blot results revealed the reduced expression of p53 protein in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone. Expression of total BAD protein was not affected by doxorubicin and cAMP-elevating agents. However, phosphorylation of BAD protein was induced in the presence of cAMP-elevating agents. Our study suggests that elevated cAMP levels inhibit doxorubicin-induced apoptosis in pre-B ALL cells through induction of BAD phosphorylation and abrogation of p53 accumulation.

  17. Synergistic Antitumor Effect of Doxorubicin and Tacrolimus (FK506 on Hepatocellular Carcinoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Francesca Capone

    2014-01-01

    Full Text Available Hepatocellular carcinoma is the fifth most common cancer worldwide and shows a complex clinical course, poor response to pharmacological treatment, and a severe prognosis. Thus, the aim of this study was to investigate whether tacrolimus (FK506 has synergistic antitumor effects with doxorubicin on two human hepatocellular carcinoma cell lines, Huh7 and HepG2. Cell viability was analyzed by Sulforhodamine B assay and synergic effect was evaluated by the software CalcuSyn. Cell apoptosis was evaluated using Annexin V and Dead Cell assay. Apoptosis-related protein PARP-1 cleaved and autophagy-related protein expressions (Beclin-1 and LC3B were measured by western blotting analysis. Cytokines concentration in cellular supernatants after treatments was studied by Bio-Plex assay. Interestingly the formulation with doxorubicin and tacrolimus induced higher cytotoxicity level on tumor cells than single treatment. Moreover, our results showed that the mechanisms involved were (i a strong cell apoptosis induction, (ii contemporaneous decrease of autophagy activation, understood as prosurvival process, and (iii downregulation of proinflammatory cytokines. In conclusion, future studies could relate to the doxorubicin/tacrolimus combination effects in mice models bearing HCC in order to see if this formulation could be useful in HCC treatment.

  18. The History of Target-Controlled Infusion

    NARCIS (Netherlands)

    Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

  19. Micellar modified spectrophotometric determination of nitrobenzenes based upon reduction with tin(II), diazotisation and coupling with the Bratton-Marshall reagent.

    Science.gov (United States)

    Escrig-Tena, I; Alvarez Rodríguez, L; Esteve-Romero, J; García-Alvarez-Coque, M C

    1998-09-01

    Nitrobenzenes, such as the antibiotic chloramphenicol, the vasodilator nicardipine, and the herbicides dinitramin, dinobuton, fenitrothion, methylparathion, oxyfluorfen, parathion, pendimethalin, quintozene, and trifluralin, were determined by using a spectrophotometric method in the visible region (540 nm). The method was based on the reduction of the nitrobenzenes to arylamines with tin(II) chloride, diazotisation of the arylamines and coupling of the diazonium ions with the Bratton-Marshall reagent. The two latter reactions were performed in a micellar medium of sodium dodecyl sulphate. The linear calibration range was 2x10(-6) to 7x10(-5) M (r>0.999), with limits of detection in the 10(-7) M level, which is 2-6 fold lower with respect to the corresponding spectrophotometric procedure in non-micellar medium. The procedure was applied to the analysis of the compounds in commercial preparations (pharmaceuticals and herbicide formulations) and in water samples, with good recoveries.

  20. Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

    Science.gov (United States)

    Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

    2017-05-01

    Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

  1. Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer.

    Science.gov (United States)

    Lv, Li; Liu, Chunxia; Chen, Chuxiong; Yu, Xiaoxia; Chen, Guanghui; Shi, Yonghui; Qin, Fengchao; Ou, Jiebin; Qiu, Kaifeng; Li, Guocheng

    2016-05-31

    The combination of a chemotherapeutic drug with a chemosensitizer has emerged as a promising strategy for cancers showing multidrug resistance (MDR). Herein we describe the simultaneous targeted delivery of two drugs to tumor cells by using biotin-decorated poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles encapsulating the chemotherapeutic drug doxorubicin and the chemosensitizer quercetin (BNDQ). Next, the potential ability of BNDQ to reverse MDR in vitro and in vivo was investigated. Studies demonstrated that BNDQ was more effectively taken up with less efflux by doxorubicin-resistant MCF-7 breast cancer cells (MCF-7/ADR cells) than by the cells treated with the free drugs, single-drug-loaded nanoparticles, or non-biotin-decorated nanoparticles. BNDQ exhibited clear inhibition of both the activity and expression of P-glycoprotein in MCF-7/ADR cells. More importantly, it caused a significant reduction in doxorubicin resistance in MCF-7/ADR breast cancer cells both in vitro and in vivo, among all the groups. Overall, this study suggests that BNDQ has a potential role in the treatment of drug-resistant breast cancer.

  2. Micellar induced regioselectivity in the two-step consecutive reaction of SO3(2-) with Br-(CH2CH2)n-Br (n=2-5).

    Science.gov (United States)

    Currie, Fredrik; Jarvoll, Patrik; Holmberg, Krister; Romsted, Laurence S; Gunaseelan, Krishnan

    2007-08-15

    High field (800 MHz) (1)H NMR was used to monitor the two-step consecutive reaction of excess SO(3)(2-) with symmetrical bifunctional alpha,omega-dibromoalkanes with butane (DBB), hexane (DBH), octane (DBO), and decane (DBD) chains in CTAB micelles at 25 degrees C. The first-order rate constant for the first substitution step for DBB and DBH is about 5 times faster than for the second, but the kinetics for DBO and DBD were not cleanly first-order. After 40 min, the solution contained about 80% of the intermediate bromoalkanesulfonate from DBB and DBH and the remainder is alkanedisulfonate and unreacted starting material. The same reactions were carried out in homogeneous MeOH/D(2)O solutions at 50 degrees C. The rate constants for all four alpha,omega-dibromoalkanes were first-order throughout the time course of the reaction and the same within +/-10%. However, because micellar solutions are organized on the nanoscale and bring together lipophilic and hydrophilic reactants into a small reaction volume at the micellar interface, they speed this substitution reaction considerably compared to reaction in MeOH/D(2)O. The CTAB micelles also induce a significant regioselectivity in product formation by speeding the first step of the consecutive reaction more than the second. The results are consistent with the bromoalkanesulfonate intermediates having a radial orientation within the micelles with the -CH(2)SO(3)(-) group in the interfacial region and the -CH(2)Br group directed into the micellar core such that the concentration of -CH(2)Br groups in the reactive zone, i.e., the micellar interface, is significantly reduced. These results provide the first example of self-assembled surfactant system altering the relative rates of the reaction steps of a consecutive reaction and, in doing so, enhancing monosubstitution of a symmetrically disubstituted species.

  3. An experimental study on the influence of infusion speed on the early mechanism of embolic effect of arterially infused absolute Ethanol in the rat

    International Nuclear Information System (INIS)

    Han, Joon Koo; Kim, Woo Ho; Lee, Byung Hee; Park, Kil Sun; Park, Jae Hyung; Kim, Chu Wan; Han, Man Chung

    1990-01-01

    In order to clarify the early mechanism of action of the tissue necrosis induced by intraarterially infused absolute ethanol, abdominal aortography and histopathologic examination after absolute ethanol infusion into aorta at fast (0.4ml/sec) and slow speed (0.04ml/sec) were performed on 22 rats (2 controls, 7 in fast infusion group, 7 in slow infusion group, 3 in fast and 3 in slow infusion groups during aorta compression, respectively). Histopathologic features under the light and scanning electron microscope were correlated with the angiographic findings within 30 minutes after ethanol infusion. The results are as follows : 1. In fast infusion group, histopathologic examination of the kidney showed severe glomerular and tubular damage. Extensive damage on endothelial and medial layer was noted in arteries, and fresh thrombi originated from the damaged arterial wall were seen. 2. Angiographic findings in the fast infusion group were luminal irregularity and early obstruction of large arteries. And circulation time was prolonged. 3. In slow infusion group, histopathologic examination of the kidney showed focal area of severe glomerular and tubular damage on relatively normal background. Endothelial and muscular damage was noted in arteries, but the degree of the damage was less severe than that of the fast infusion group. 4. Angiographic findings in the slow infusion group were focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but obstruction of the major arteries was not seen

  4. Infusing Systems Thinking into Career Counseling

    Science.gov (United States)

    Ryan, Charles W.; Tomlin, James H.

    2010-01-01

    This study examined the role of career counselors in infusing systems thinking into occupational advising. The authors conducted a qualitative review and analysis of selected literature on systems thinking and analyzed trends for adaptation to career counseling practice. This analysis suggests that career counselors need to infuse systems…

  5. Multiple sessions of liposomal doxorubicin delivery via focused ultrasound mediated blood-brain barrier disruption: a safety study.

    Science.gov (United States)

    Aryal, Muna; Vykhodtseva, Natalia; Zhang, Yong-Zhi; McDannold, Nathan

    2015-04-28

    Transcranial MRI-guided focused ultrasound is a rapidly advancing method for delivering therapeutic and imaging agents to the brain. It has the ability to facilitate the passage of therapeutics from the vasculature to the brain parenchyma, which is normally protected by the blood-brain barrier (BBB). The method's main advantages are that it is both targeted and noninvasive, and that it can be easily repeated. Studies have shown that liposomal doxorubicin (Lipo-DOX), a chemotherapy agent with promise for tumors in the central nervous system, can be delivered into the brain across BBB. However, prior studies have suggested that doxorubicin can be significantly neurotoxic, even at small concentrations. Here, we studied whether multiple sessions of Lipo-DOX administered after FUS-induced BBB disruption (FUS-BBBD) induces severe adverse events in the normal brain tissues. First, we used fluorometry to measure the doxorubicin concentrations in the brain after FUS-BBBD to ensure that a clinically relevant doxorubicin concentration was achieved in the brain. Next, we performed three weekly sessions with FUS-BBBD±Lipo-DOX administration. Five to twelve targets were sonicated each week, following a schedule described previously in a survival study in glioma-bearing rats (Aryal et al., 2013). Five rats received three weekly sessions where i.v. injected Lipo-DOX was combined with FUS-BBBD; an additional four rats received FUS-BBBD only. Animals were euthanized 70days from the first session and brains were examined in histology. We found that clinically-relevant concentrations of doxorubicin (4.8±0.5μg/g) were delivered to the brain with the sonication parameters (0.69MHz; 0.55-0.81MPa; 10ms bursts; 1Hz PRF; 60s duration), microbubble concentration (Definity, 10μl/kg), and the administered Lipo-DOX dose (5.67mg/kg) used. The resulting concentration of Lipo-DOX was reduced by 32% when it was injected 10min after the last sonication compared to cases where the agent was

  6. Is continuous infusion of imipenem always the best choice?

    Science.gov (United States)

    Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

    2017-03-01

    Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT >MIC , 40%fT >MIC and 100%fT >MIC . For the target of 40%fT >MIC , all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT >MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT >MIC and 100%fT >MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  7. Simultaneous Extraction, Enrichment and Removal of Dyes from Aqueous Solutions Using a Magnetic Aqueous Micellar Two-Phase System

    Directory of Open Access Journals (Sweden)

    Shuanggen Wu

    2017-12-01

    Full Text Available The magnetic aqueous micellar two-phase system (MAMTPS has the advantages combined of magnetic solid phase extraction (MSPE and aqueous micellar two-phase system (AMTPS. Thus, MAMTPS based on Fe3O4 magnetic nanoparticles (MNPs and a nonionic surfactant Triton X-114 (TX-114 was developed for the extraction, enrichment and removal of three dyes (Congo red, methyl blue, and methyl violet from aqueous solutions in this study. The MNPs Fe3O4@NH2 was screened as the optimal MNPs benefiting the extraction. Then, the influencing factors of MNPs amount, TX-114 concentration, vibration time, and extraction temperature were investigated in detail. The results showed that the extraction efficiencies of three dyes almost reached 100% using MAMTPS under the optimal conditions; MAMTPS had higher extraction ability than the individual MSPE or AMTPS. Thus, MAMTPS had the advantages of simple operation, high extraction ability, easy recycling of MNPs, and short phase-separation time, which showspotential for use in the extraction and analysis of contaminants from water samples.

  8. Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

    Directory of Open Access Journals (Sweden)

    Ashraf H. ElGhandour

    2009-04-01

    Full Text Available Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin’s lymphoma (NHL may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP, not exceeding the total allowed dose of doxorubicin (500 mg/m2. Ten healthy controls were included in our study. Human heart-type fatty acid binding protein (H-FABP was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

  9. An Asymptotic Theory for the Re-Equilibration of a Micellar Surfactant Solution

    KAUST Repository

    Griffiths, I. M.; Bain, C. D.; Breward, C. J. W.; Chapman, S. J.; Howell, P. D.; Waters, S. L.

    2012-01-01

    Micellar surfactant solutions are characterized by a distribution of aggregates made up predominantly of premicellar aggregates (monomers, dimers, trimers, etc.) and a region of proper micelles close to the peak aggregation number, connected by an intermediate region containing a very low concentration of aggregates. Such a distribution gives rise to a distinct two-timescale reequilibration following a system dilution, known as the t1 and t2 processes, whose dynamics may be described by the Becker-Döring equations. We use a continuum version of these equations to develop a reduced asymptotic description that elucidates the behavior during each of these processes.© 2012 Society for Industrial and Applied Mathematics.

  10. Self-association of analgesics in aqueous solution: micellar properties of dextropropoxyphene hydrochloride and methadone hydrochloride.

    Science.gov (United States)

    Attwood, D; Tolley, J A

    1980-08-01

    The solution properties of several analgesics including dextropropoxyphene hydrochloride, methadone hydrochloride, dextromoramide acid tartrate and dipipanone hydrochloride have been examined using light scattering, conductivity, vapour pressure osmometry and surface tension techniques. A micellar pattern of association was established for dextropropoxyphene hydrochloride and methadone hydrochloride and critical micelle concentrations and aggregation numbers are reported. The hydrophobic contribution to the free energy of micellization of dextropropoxyphene was determined from measurement of the critical micelle concentration in the presence of added electrolyte.

  11. Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines

    Science.gov (United States)

    Ghafari, Fereshteh; Rajabi, Mohammad Reza; Mazoochi, Tahereh; Taghizadeh, Mohsen; Nikzad, Hossein; Atlasi, Mohammad Ali; Taherian, Aliakbar

    2017-03-01

    Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10μg/mL of Arctium lappa root extract and 5 μM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies. Creative Commons Attribution License

  12. Krypton 81m infusion studies. Chapter 18

    International Nuclear Information System (INIS)

    Kaplan, E.; Mayron, L.W.; Friedman, A.M.; Gindler, J.E.

    1978-01-01

    A technique is described to give a continuous, constant-rate, intravascular infusion of 81 Krsup(m). Modifications of earlier generators included production of sodium-free 81 Rb, the use of a solution of commercial sterile isotonic non-ionic 5% dextrose-in-water as an eluant, the incorporation of a constant-rate infusion pump, and the miniaturization of the generator column and catheter system. Results are presented of studies of 81 Krsup(m) distribution in dogs, using both intravenous and intra-arterial infusion. (author)

  13. Therapeutic Efficacy of Orally Delivered Doxorubicin Nanoparticles in Rat Tongue Cancer Induced by 4-Nitroquinoline 1-Oxide

    Directory of Open Access Journals (Sweden)

    Monir Moradzadeh Khiavi

    2015-06-01

    Full Text Available Purpose: Oral cancer is one of the most significant cancers in the world, and squamous cell carcinoma makes up about 94% of oral malignancies. The aim of the present study was to compare the efficacy of doxorubicin plus methotrexate - loaded nanoparticles on tongue squamous cell carcinoma induced by 4NQO and compare it with the commercial doxorubicin and methotrexate delivered orally on seventy SD male rats. Methods: 70 rats were divided into five groups. During the study, the animals were weighed by a digital scale once a week. Number of mortalities was recorded in the data collection forms. At the end of the treatment, biopsy samples were taken from rat tongues in order to evaluate the severity of dysplasia and the extent of cell proliferation. The results were analyzed using ANOVA, descriptive statistics and chi-square test. Results: No statistically significant difference was found in the mean weight of five groups (p>0.05. No significant relationship was found between groups and mortality rate (P = 0. 39. In addition, there was a significant relationship between groups and the degree of dysplasia (P <0.001. The statistical analysis showed a significant relationship between groups and the rate of cell proliferation (p <0.001. Conclusion: The results of the present study showed that the use of doxorubicin plus methotrexate - loaded nanoparticles orally had more therapeutic effects than commercial doxorubicin plus methotrexate.

  14. The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes.

    Directory of Open Access Journals (Sweden)

    Olga Alster

    Full Text Available Nibrin plays an important role in the DNA damage response (DDR and DNA repair. DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether truncated nibrin (p70, causing Nijmegen Breakage Syndrome (NBS, is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3R spontaneously immortalized T cell lines from NBS patients, with the founding mutation and a control cell line (L5. S4 and S3R cells have the same level of p70 nibrin, however p70 from S4 cells was able to form more complexes with ATM and BRCA1. Doxorubicin-induced DDR followed by cell senescence could only be observed in L5 and S4 cells, but not in the S3R ones. Furthermore the S3R cells only underwent cell death, but not senescence after doxorubicin treatment. In contrary to doxorubicin treatment, cells from all three cell lines were able to activate the DDR pathway after being exposed to γ-radiation. Downregulation of nibrin in normal human vascular smooth muscle cells (VSMCs did not prevent the activation of DDR and induction of senescence. Our results indicate that a substantially reduced level of nibrin or its truncated p70 form is sufficient to induce DNA-damage dependent senescence in VSMCs and S4 cells, respectively. In doxorubicin-treated S3R cells DDR activation was severely impaired, thus preventing the induction of senescence.

  15. Determination of adulteration of malachite green in green pea and some prepared foodstuffs by micellar liquid chromatography.

    Science.gov (United States)

    Ashok, Vipin; Agrawal, Nitasha; Durgbanshi, Abhilasha; Esteve-Romero, Josep; Bose, Devasish

    2014-01-01

    A simple, fast, and robust micellar LC method was developed for the separation and identification of the nonpermitted color malachite green in green pea and some ready-to-eat foodstuffs. Malachite green (4-[(4-dimethylaminophenyl) phenyl-methyl]-N,N-dimethylaniline) is a hazardous dye that is used to treat fungal and protozoan infections in fish and is a common adulterant (coloring agent) in green pea and other green vegetables because of its green color. In the present work, malachite green was determined in various foodstuffs using a direct injection technique on an RP C18 column with isocratic elution. The optimum mobile phase consisted of 0.15 M sodium dodecyl sulfate (SDS), 6% pentanol buffered at pH 5. Detection was carried out at 620 nm. Malachite green was eluted in 9.2 min without any interference caused by endogenous compounds. Linearities (r > 0.9999), intraday and interday precision (RSD less than 1.00%) in micellar media, and robustness were studied for method validation. LOD and LOQ were 0.10 and 0.25 ppm, respectively. The simplicity of the developed method makes it useful for routine analysis in the area of food QC.

  16. Prediction of retention in micellar electrokinetic chromatography based on molecular structural descriptors by using the heuristic method

    International Nuclear Information System (INIS)

    Liu Huanxiang; Yao Xiaojun; Liu Mancang; Hu Zhide; Fan Botao

    2006-01-01

    Based on calculated molecular descriptors from the solutes' structure alone, the micelle-water partition coefficients of 103 solutes in micellar electrokinetic chromatography (MEKC) were predicted using the heuristic method (HM). At the same time, in order to show the influence of different molecular descriptors on the micelle-water partition of solute and to well understand the retention mechanism in MEKC, HM was used to build several multivariable linear models using different numbers of molecular descriptors. The best 6-parameter model gave the following results: the square of correlation coefficient R 2 was 0.958 and the mean relative error was 3.98%, which proved that the predictive values were in good agreement with the experimental results. From the built model, it can be concluded that the hydrophobic, H-bond, polar interactions of solutes with the micellar and aqueous phases are the main factors that determine their partitioning behavior. In addition, this paper provided a simple, fast and effective method for predicting the retention of the solutes in MEKC from their structures and gave some insight into structural features related to the retention of the solutes

  17. Insulin Protects against Brain Oxidative Stress with an Apparent Effect on Episodic Memory in Doxorubicin-Induced Cognitive Dysfunction in Wistar Rats.

    Science.gov (United States)

    Ramalingayya, Grandhi Venkata; Sonawane, Vishwajeet; Cheruku, Sri Pragnya; Kishore, Anoop; Nayak, Pawan G; Kumar, Nitesh; Shenoy, Rekha S; Nandakumar, Krishnadas

    2017-01-01

    The present study was aimed at assessing the protective effect of insulin against doxorubicin (DOX)-induced cognitive dysfunction in Wistar rats. Cognitive function for episodic memory was assessed by a novel object recognition task (NORT) in male Wistar rats. Oxidative stress markers-SOD, catalase, glutathione, and lipid peroxidation-in the hippocampus and frontal cortex were assessed using colorimetric methods. Doxorubicin treatment (2.5 mg/kg, i.p., every 5 days for 50 days) reduced recognition and discriminative indices in NORT with increased oxidative stress in the brain. A nonhypoglycemic dose of insulin (0.5 IU/kg, i.p.) significantly reduced brain oxidative stress (MDA) induced by doxorubicin with an increase in the antioxidant defense systems (SOD, catalase, and GSH). Rats treated with combined insulin and DOX spent comparatively more time with the novel object when compared to the non-novel objects; however, the observed difference was not statistically significant. An apparent improvement (p insulin reduces brain oxidative stress and apparently improves doxorubicin-induced cognitive dysfunction in Wistar rats.

  18. p38 MAPK and JNK antagonistically control senescence and cytoplasmic p16INK4A expression in doxorubicin-treated endothelial progenitor cells.

    Directory of Open Access Journals (Sweden)

    Paolo Spallarossa

    Full Text Available Patients treated with low-dose anthracyclines often show late onset cardiotoxicity. Recent studies suggest that this form of cardiotoxicity is the result of a progenitor cell disease. In this study we demonstrate that Cord Blood Endothelial Progenitor Cells (EPCs exposed to low, sub-apoptotic doses of doxorubicin show a senescence phenotype characterized by increased SA-b-gal activity, decreased TRF2 and chromosomal abnormalities, enlarged cell shape, and disarrangement of F-actin stress fibers accompanied by impaired migratory ability. P16( INK4A localizes in the cytoplasm of doxorubicin-induced senescent EPCs and not in the nucleus as is the case in EPCs rendered senescent by different stimuli. This localization together with the presence of an arrest in G2, and not at the G1 phase boundary, which is what usually occurs in response to the cell cycle regulatory activity of p16(INK4A, suggests that doxorubicin-induced p16( INK4A does not regulate the cell cycle, even though its increase is closely associated with senescence. The effects of doxorubicin are the result of the activation of MAPKs p38 and JNK which act antagonistically. JNK attenuates the senescence, p16( INK4A expression and cytoskeleton remodeling that are induced by activated p38. We also found that conditioned medium from doxorubicin-induced senescent cardiomyocytes does not attract untreated EPCs, unlike conditioned medium from apoptotic cardiomyocytes which has a strong chemoattractant capacity. In conclusion, this study provides a better understanding of the senescence of doxorubicin-treated EPCs, which may be helpful in preventing and treating late onset cardiotoxicity.

  19. Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Bang Soo-Mee

    2006-01-01

    Full Text Available Abstract Background Although numerous chemotherapeutic agents have been tested, the role of systemic chemotherapy for hepatocellular carcinoma (HCC has not been clarified. New therapeutic strategies are thus needed to improve outcomes, and we designed this study with new effective drug combination. Methods Twenty-nine patients with histologically-confirmed, metastatic HCC received a combination chemotherapy with doxorubicin 60 mg/m2 and cisplatin 60 mg/m2 on day 1, plus capecitabine 2000 mg/m2/day as an intermittent regimen of 2 weeks of treatment followed by a 1-week rest. Results The median age was 49 years (range, 32–64 and 19 patients were hepatitis B virus seropositive. Child-Pugh class was A in all patients and 4 had Zubrod performance status of 2. The objective response rate was 24% (95% CI 9–40 with 6 stable diseases. The chemotherapy was generally well tolerated despite one treatment-related death. Conclusion Combination chemotherapy with doxorubicin, cisplatin and capecitabine produced modest antitumor activity with tolerable adverse effects in patients with metastatic HCC.

  20. Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy.

    Science.gov (United States)

    Sanson, Charles; Diou, Odile; Thévenot, Julie; Ibarboure, Emmanuel; Soum, Alain; Brûlet, Annie; Miraux, Sylvain; Thiaudière, Eric; Tan, Sisareuth; Brisson, Alain; Dupuis, Vincent; Sandre, Olivier; Lecommandoux, Sébastien

    2011-02-22

    Hydrophobically modified maghemite (γ-Fe(2)O(3)) nanoparticles were encapsulated within the membrane of poly(trimethylene carbonate)-b-poly(l-glutamic acid) (PTMC-b-PGA) block copolymer vesicles using a nanoprecipitation process. This formation method gives simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with good control over the vesicles size (100-400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation. The deformation of the vesicle membrane under an applied magnetic field has been evidenced by small angle neutron scattering. These superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for magnetic resonance imaging. They can also be guided in a magnetic field gradient. The feasibility of controlled drug release by radio frequency magnetic hyperthermia was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of magneto-chemotherapy. These magnetic polymersomes can be used as efficient multifunctional nanocarriers for combined therapy and imaging.

  1. Canadian Palliative Community Milrinone Infusions: A Case Series.

    Science.gov (United States)

    Reimche, Ruthanne; Salcedo, Daniel

    2016-01-01

    Abstract Symptom managementfor end-of-life heartfailure (HF) patients is a significant concern. Currently, Canadian practice does not support community milrinone therapy in end-of-life HF patients. Two patients had severe HF that was unresponsive to optimal medications. Further optimization and furosemide infusions were ineffective for symptom management. Both patients' symptoms were better controlled with optimal medication, furosemide, and milrinone infusions. A tailored discharge plan was developed to assist with community milrinone infusions. We discuss the challenges and successes of transitioning two patients to the community. By providing symptom management and meaningful patient and family experience, both patients were able to die in a setting of their choosing. Milrinone infusions as a bridge to end of life may improve symptoms and quality of life. Select patients may benefit from milrinone infusions with resources put in place; these end-of-life HF patients can be supported in the community.

  2. Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Ryu, Chang Seon; Kwak, Hui Chan; Lee, Kye Sook; Kang, Keon Wook; Oh, Soo Jin; Lee, Ki Ho; Kim, Hwan Mook; Ma, Jin Yeul; Kim, Sang Kyum

    2011-01-01

    Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to ∼ 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase, and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism. - Research highlights: → MCF-7/Adr cells showed decreases in cellular GSH

  3. The different-ligand complexing of europium with complexones and β-diketones in micellar solution

    International Nuclear Information System (INIS)

    Svetlova, I.E.; Dobrynina, N.A.; Smirnova, N.S.; Martynenko, L.I.; Evseev, A.M.; Savitskij, A.P.

    1989-01-01

    Method of pH-metric titration with mathematical simulation was used to study the effect of nonionic surfactant (polyoxyethyleneoctylphenyl este) on stability of europium complexes with cyclohexanediaminetetraacetic and ethylenediaminetetraacetic acids. Optimal conditions for ternary complex formation in the system Eu 3+ -complexone-β-diketone at pH 7.0-9.0 were found. Complex-compositions were determined and their stability constants were calculated. It is shown that complex stability decreases by several orders in micellar solutions, tecause β-diketone introduction to the solution decreases thermodynamic stability of complexes

  4. The management of non-invasive bladder tumours with Doxorubicin intravesical instillation after transurethral resection.

    Science.gov (United States)

    Al-Gallab, Musa I; Naddaf, Louai A; Kanan, Mohamad R

    2009-04-01

    Evaluation of the intravesical instillation of doxorubicin for its effect on disease recurrence for patients with non-invasive bladder tumour. The study was performed at Al Assad University Hospital in Lattakia, Syria and included patients with non-invasive bladder tumours who were managed with transurethral resection and induction and maintenance therapy with intravesical doxorubicin. They were followed up by cystoscopy every 3 months for 2 years and every 6 months thereafter with special emphasis on recurrence rates. The study included 85 patients with non-invasive bladder tumours: 23 with non-invasive papillary carcinoma (Stage Ta), 62 with tumour invading subepithelial connective tissue (Stage T1). Twelve patients had well differentiated tumours (Grade 1), 48 had moderately differentiated (Grade 2), 25 had poorly differentiated (Grade 3) tumours. The total recurrence rate was 23%. The rates of recurrence were 56% in Grade 3 and 0% in Grade 1. The recurrence rate was 41% in patients with large tumours versus 17% in those with small tumours; 44% in those with multiple tumours compared to 18% in those with solitary tumours; 30% of Stage Ta tumours recurred and 21% of Stage T1 tumours. In short term follow-up, our rate of recurrence was 23%. Adjuvant intravesical doxorubicin was shown to reduce the recurrence of superficial bladder cancer. Tumour grade, size and number were shown to be prognostic factors for recurrence.

  5. A new infusion pathway intactness monitoring system.

    Science.gov (United States)

    Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Ninomiya, Ishio; Sata, Koji; Hamada, Shingo; Caldwell, W Morton

    2006-01-01

    A new infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. An AC (alternating current) voltage is induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. The induced AC voltage can be recorded by a main electrode wrapped around the infusion polyvinyl chloride tube. A reference electrode is wrapped on the electrode to monitor the AC voltage around the main electrode. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

  6. Comparison of the intracoronary continuous infusion method using a microcatheter and the intravenous continuous adenosine infusion method for inducing maximal hyperemia for fractional flow reserve measurement.

    Science.gov (United States)

    Yoon, Myeong-Ho; Tahk, Seung-Jea; Yang, Hyoung-Mo; Park, Jin-Sun; Zheng, Mingri; Lim, Hong-Seok; Choi, Byoung-Joo; Choi, So-Yeon; Choi, Un-Jung; Hwang, Joung-Won; Kang, Soo-Jin; Hwang, Gyo-Seung; Shin, Joon-Han

    2009-06-01

    Inducing stable maximal coronary hyperemia is essential for measurement of fractional flow reserve (FFR). We evaluated the efficacy of the intracoronary (IC) continuous adenosine infusion method via a microcatheter for inducing maximal coronary hyperemia. In 43 patients with 44 intermediate coronary lesions, FFR was measured consecutively by IC bolus adenosine injection (48-80 microg in left coronary artery, 36-60 microg in the right coronary artery) and a standard intravenous (IV) adenosine infusion (140 microg x min(-1) x kg(-1)). After completion of the IV infusion method, the tip of an IC microcatheter (Progreat Microcatheter System, Terumo, Japan) was positioned at the coronary ostium, and FFR was measured with increasing IC continuous adenosine infusion rates from 60 to 360 microg/min via the microcatheter. Fractional flow reserve decreased with increasing IC adenosine infusion rates, and no further decrease was observed after 300 microg/min. All patients were well tolerated during the procedures. Fractional flow reserves measured by IC adenosine infusion with 180, 240, 300, and 360 microg/min were significantly lower than those by IV infusion (P < .05). Intracoronary infusion at 180, 240, 300, and 360 microg/min was able to shorten the times to induction of optimal and steady-stable hyperemia compared to IV infusion (P < .05). Functional significances were changed in 5 lesions by IC infusion at 240 to 360 microg/min but not by IV infusion. The results of this study suggest that an IC adenosine continuous infusion method via a microcatheter is safe and effective in inducing steady-state hyperemia and more potent and quicker in inducing optimal hyperemia than the standard IV infusion method.

  7. Inhibition of endogenous lactate turnover with lactate infusion in humans

    International Nuclear Information System (INIS)

    Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C.

    1989-01-01

    The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U- 14 C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production

  8. Biodegradable star HPMA polymer conjugates of doxorubicin for passive tumor targeting

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Strohalm, Jiří; Chytil, Petr; Černoch, Peter; Starovoytova, Larisa; Pechar, Michal; Ulbrich, Karel

    2011-01-01

    Roč. 42, č. 5 (2011), s. 527-539 ISSN 0928-0987 R&D Projects: GA AV ČR IAA400500806; GA AV ČR IAAX00500803; GA ČR GA203/08/0543 Institutional research plan: CEZ:AV0Z40500505 Keywords : dendrimer * HPMA copolymers * doxorubicin Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.212, year: 2011

  9. Removal of Pyrethrin from Aqueous Effluents by Adsorptive Micellar Flocculation

    Directory of Open Access Journals (Sweden)

    Pardon K. Kuipa

    2015-01-01

    Full Text Available The equilibrium adsorption of pyrethrin onto aggregates formed by the flocculation of micelles of the surfactant sodium dodecyl sulphate (SDS with aluminium sulphate is reported. The experimental results were analysed using different adsorption isotherms (Langmuir, Freundlich, Redlich-Peterson, Sips, Radke-Prausnitz, Temkin, linear equilibrium, and the Dubin-Radushkevich isotherms. The Freundlich and linear equilibrium isotherms best describe the adsorption of pyrethrin onto SDS micellar flocs, with the Freundlich adsorption constant, KF, and the mass distribution coefficient, KD, of 64.266 ((mg/g(L/mg1/n and 119.65 L/g, respectively. Applicability of the Freundlich adsorption model suggests that heterogeneous surface adsorption affects the adsorption. The mean free energy value estimated using the Dubinin-Radushkevich isotherm was 0.136 kJ/mol indicating that physisorption may be predominant in the adsorption process.

  10. Síndrome da infusão do propofol Síndrome de la infusión del propofol Propofol infusion syndrome

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2007-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A síndrome da infusão do propofol tem sido descrita como uma síndrome rara e quase sempre fatal que ocorre após infusão prolongada desse fármaco. Ela pode resultar em acidose metabólica grave, rabdomiólise, colapso cardiovascular e morte. O objetivo deste artigo foi mostrar aspectos relacionados com a síndrome da infusão do propofol por meio da revisão de literatura. CONTEÚDO: Estão definidas as características da síndrome da infusão do propofol quanto à fisiopatologia, características clínicas, tratamento e recomendações de dose para pacientes gravemente enfermos. CONCLUSÕES: O propofol deve ser usado com cautela quando se planeja seu uso sob regime de infusão contínua por períodos prolongados. O surgimento de sinais sugestivos da síndrome da infusão do propofol indica a suspensão imediata do fármaco e início de medidas de suporte.JUSIFICATIVA Y OBJETIVOS: El síndrome de la infusión del propofol ha sido descrito como un síndrome raro y frecuentemente fatal que ocurre después de la infusión prolongada de ese fármaco. Puede resultar en acidez metabólica grave, rabdomiólisis, colapso cardiovascular y deceso. El objetivo de este artículo fue mostrar aspectos relacionados al síndrome de la infusión del propofol a través de la revisión de la literatura. CONTENIDO: Están definidas las características del síndrome de la infusión del propofol en cuanto a la fisiopatología, características clínicas, tratamiento y recomendaciones de dosis para pacientes gravemente enfermos. CONCLUSIONES: El propofol debe ser usado con cautela cuando se planea su uso bajo el régimen de infusión continua por períodos prolongados. El aparecimiento de señales sugestivas del síndrome de la infusión del propofol indica la suspensión inmediata del fármaco y el inicio de medidas de soporte.BACKGROUND AND OBJECTIVES: Propofol infusion syndrome has been described as a rare, and frequently fatal

  11. Survey of the effect of doxorubicin and flavonoid extract of white Morus alba leaf on apoptosis induction in a-172 GBM cell line.

    Science.gov (United States)

    Dabili, Sheyda; Fallah, Soudabeh; Aein, Mojdeh; Vatannejad, Akram; Panahi, Ghodratollah; Fadaei, Reza; Moradi, Nariman; Shojaii, Asie

    2018-02-20

    In this study, the effect of doxorubicin, flavonoid extract of white Morus alba leaf (MFE) and a combination of doxorubicin and flavonoid extract on Bax and Bcl2 levels and caspase 3 activity of cancer A-172 GBM cell line was investigated. Bax/Bcl2 levels of treated A-172 GBM cell line with flavonoid extract of white mulberry leaf were estimated by ELISA methods. Caspase 3 activity of treated A-172 GBM cells was determined by calorimetric assay. The flow cytometry assessment was used to estimate the apoptosis percent of treated A-172 GBM cells. Treatment of A-172 GBM cells with MFE, doxorubicin and a combination of MFE and doxorubicin caused a significant decrease in Bcl2 level and an increase in Bax level. The apoptosis percent of treated cells were also elevated significantly. Present results suggest that concomitant use of herbal medicine and chemotherapy may be an effective alternative method for the treatment of cancers.

  12. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    International Nuclear Information System (INIS)

    Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

    2010-01-01

    Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes

  13. Effect of Insulin Infusion on Liver Protein Synthesis during Hemodialysis

    DEFF Research Database (Denmark)

    Reinhard, Mark; Frystyk, Jan; Jespersen, Bente

    2011-01-01

    Background Hemodialysis (HD) is a catabolic procedure that may contribute to the high frequency of protein-energy wasting among patients receiving maintenance HD. The present study investigated the additional effect of glucose and glucose-insulin infusion on liver protein synthesis during HD...... compared with a meal alone. Methods In a randomized cross-over study with three arms, 11 non-diabetic HD patients were assigned to receive a conventional HD session with either: • no treatment (NT) • IV infusion of glucose (G) • IV infusion of glucose-insulin (GI) During infusions blood glucose levels were...... maintained at 8.0-10.0 mmol/L by additional glucose infusion. Glucose and glucose-insulin infusions were commenced 2 h prior to HD and continued throughout the HD session. Fasting blood samples were collected at baseline before infusion and followed by the only meal allowed during the study. Results Blood...

  14. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

    Science.gov (United States)

    Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

    2016-01-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

  15. Protolytic properties and complexation of DL-alpha-alanine and DL-alpha-valine and their dipeptides in aqueous and micellar solutions of surfactants

    NARCIS (Netherlands)

    Chernyshova, O. S.; Boychenko, Oleksandr; Abdulrahman, H.; Loginova, L. P.

    In this work we investigated the effect of the micellar media of anionic (sodium dodecylsulfate, SDS), cationic (cetylpiridinium chloride, CPC) and non-ionic (Brij-35) surfactants on the protolytic properties of amino acids DL-alpha-alanine, DL-alpha-valine and dipeptides

  16. Thermodynamics of Micellar Systems : Comparison of Mass Action and Phase Equilibrium Models for the Calculation of Standard Gibbs Energies of Micelle Formation

    NARCIS (Netherlands)

    Blandamer, Michael J.; Cullis, Paul M.; Soldi, L. Giorgio; Engberts, Jan B.F.N.; Kacperska, Anna; Os, Nico M. van

    1995-01-01

    Micellar colloids are distinguished from other colloids by their association-dissociation equilibrium in solution between monomers, counter-ions and micelles. According to classical thermodynamics, the standard Gibbs energy of formation of micelles at fixed temperature and pressure can be related to

  17. Lipolytic response to glucose infusion in human subjects

    International Nuclear Information System (INIS)

    Wolfe, R.R.; Peters, E.J.

    1987-01-01

    The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and [1- 13 C]palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg -1 x min -1 , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg -1 x min -1 , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg -1 x min -1 infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay

  18. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial.

    Science.gov (United States)

    Lipshultz, Steven E; Scully, Rebecca E; Lipsitz, Stuart R; Sallan, Stephen E; Silverman, Lewis B; Miller, Tracie L; Barry, Elly V; Asselin, Barbara L; Athale, Uma; Clavell, Luis A; Larsen, Eric; Moghrabi, Albert; Samson, Yvan; Michon, Bruno; Schorin, Marshall A; Cohen, Harvey J; Neuberg, Donna S; Orav, E John; Colan, Steven D

    2010-10-01

    Doxorubicin chemotherapy is associated with cardiomyopathy. Dexrazoxane reduces cardiac damage during treatment with doxorubicin in children with acute lymphoblastic leukaemia (ALL). We aimed to establish the long-term effect of dexrazoxane on the subclinical state of cardiac health in survivors of childhood high-risk ALL 5 years after completion of doxorubicin treatment. Between January, 1996, and September, 2000, children with high-risk ALL were enrolled from nine centres in the USA, Canada, and Puerto Rico. Patients were assigned by block randomisation to receive ten doses of 30 mg/m² doxorubicin alone or the same dose of doxorubicin preceded by 300 mg/m² dexrazoxane. Treatment assignment was obtained through a telephone call to a centralised registrar to conceal allocation. Investigators were masked to treatment assignment but treating physicians and patients were not; however, investigators, physicians, and patients were masked to study serum cardiac troponin-T concentrations and echocardiographic measurements. The primary endpoints were late left ventricular structure and function abnormalities as assessed by echocardiography; analyses were done including all patients with data available after treatment completion. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00165087. 100 children were assigned to doxorubicin (66 analysed) and 105 to doxorubicin plus dexrazoxane (68 analysed). 5 years after the completion of doxorubicin chemotherapy, mean left ventricular fractional shortening and end-systolic dimension Z scores were significantly worse than normal for children who received doxorubicin alone (left ventricular fractional shortening: -0·82, 95% CI -1·31 to -0·33; end-systolic dimension: 0·57, 0·21-0·93) but not for those who also received dexrazoxane (-0·41, -0·88 to 0·06; 0·15, -0·20 to 0·51). The protective effect of dexrazoxane, relative to doxorubicin alone, on left ventricular wall thickness (difference

  19. Comparison of infusion pumps calibration methods

    Science.gov (United States)

    Batista, Elsa; Godinho, Isabel; do Céu Ferreira, Maria; Furtado, Andreia; Lucas, Peter; Silva, Claudia

    2017-12-01

    Nowadays, several types of infusion pump are commonly used for drug delivery, such as syringe pumps and peristaltic pumps. These instruments present different measuring features and capacities according to their use and therapeutic application. In order to ensure the metrological traceability of these flow and volume measuring equipment, it is necessary to use suitable calibration methods and standards. Two different calibration methods can be used to determine the flow error of infusion pumps. One is the gravimetric method, considered as a primary method, commonly used by National Metrology Institutes. The other calibration method, a secondary method, relies on an infusion device analyser (IDA) and is typically used by hospital maintenance offices. The suitability of the IDA calibration method was assessed by testing several infusion instruments at different flow rates using the gravimetric method. In addition, a measurement comparison between Portuguese Accredited Laboratories and hospital maintenance offices was performed under the coordination of the Portuguese Institute for Quality, the National Metrology Institute. The obtained results were directly related to the used calibration method and are presented in this paper. This work has been developed in the framework of the EURAMET projects EMRP MeDD and EMPIR 15SIP03.

  20. Prospective Randomized Study of Doxorubicin-Eluting-Bead Embolization in the Treatment of Hepatocellular Carcinoma: Results of the PRECISION V Study

    International Nuclear Information System (INIS)

    Lammer, Johannes; Malagari, Katarina; Vogl, Thomas; Pilleul, Frank; Denys, Alban; Watkinson, Anthony; Pitton, Michael; Sergent, Geraldine; Pfammatter, Thomas; Terraz, Sylvain; Benhamou, Yves; Avajon, Yves; Gruenberger, Thomas; Pomoni, Maria; Langenberger, Herbert; Schuchmann, Marcus; Dumortier, Jerome; Mueller, Christian; Chevallier, Patrick; Lencioni, Riccardo

    2010-01-01

    Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

  1. Continuous indomethacin infusion may be less effective than bolus infusions for ductal closure in very low birth weight infants

    NARCIS (Netherlands)

    de Vries, NKS; Jagroep, FK; Jaarsma, AS; Elzenga, NJ; Bos, AF

    The effectiveness of continuous indomethacin (INDO) infusion versus bolus infusions for closure of patent ductus arteriosus (PDA) was investigated. The study design was an open-label case series (continuous INDO) with historic controls matched for gestational age (bolus INDO). Ductal closure rates

  2. Vocal fold submucosal infusion technique in phonomicrosurgery.

    Science.gov (United States)

    Kass, E S; Hillman, R E; Zeitels, S M

    1996-05-01

    Phonomicrosurgery is optimized by maximally preserving the vocal fold's layered microstructure (laminae propriae). The technique of submucosal infusion of saline and epinephrine into the superficial lamina propria (SLP) was examined to delineate how, when, and why it was helpful toward this surgical goal. A retrospective review revealed that the submucosal infusion technique was used to enhance the surgery in 75 of 152 vocal fold procedures that were performed over the last 2 years. The vocal fold epithelium was noted to be adherent to the vocal ligament in 29 of the 75 cases: 19 from previous surgical scarring, 4 from cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1 from radiotherapy. The submucosal infusion technique was most helpful when the vocal fold epithelium required resection and/or when extensive dissection in the SLP was necessary. The infusion enhanced the surgery by vasoconstriction of the microvasculature in the SLP, which improved visualization during cold-instrument tangential dissection. Improved visualization facilitated maximal preservation of the SLP, which is necessary for optimal pliability of the overlying epithelium. The infusion also improved the placement of incisions at the perimeter of benign, premalignant, and malignant lesions, and thereby helped preserve epithelium uninvolved by the disorder.

  3. Protective effects of acute exercise prior to doxorubicin on cardiac function of breast cancer patients: A proof-of-concept RCT.

    Science.gov (United States)

    Kirkham, A A; Shave, R E; Bland, K A; Bovard, J M; Eves, N D; Gelmon, K A; McKenzie, D C; Virani, S A; Stöhr, E J; Warburton, D E R; Campbell, K L

    2017-10-15

    Preclinical studies have reported that a single treadmill session performed 24h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24h prior to treatment changes this response. Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h prior to treatment (control, n=11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24-48h after the treatment. Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p≤0.01). Whereas systemic vascular resistance (pvolume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial

    DEFF Research Database (Denmark)

    Oakman, C; Francis, P A; Crown, J

    2013-01-01

    Background In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease...

  5. Ascorbyl radical disproportionation in reverse micellar systems

    Science.gov (United States)

    Gębicki, J. L.; Szymańska-Owczarek, M.; Pacholczyk-Sienicka, B.; Jankowski, S.

    2018-04-01

    Ascorbyl radical was generated by the pulse radiolysis method and observed with the fast kinetic spectrophotometry within reverse micelles stabilized by AOT in n-heptane or by Igepal CO-520 in cyclohexane at different water to surfactant molar ratio, w0. Rate constants for the disproportionation of the ascorbyl radicals were smaller than those for intermicellar exchange for both type of reverse micelles and slower than those in homogeneous aqueous solutions. However, they increased with increasing w0 for AOT/n-heptane system, while they decreased for Igepal CO-520 system. The absorption spectra of ascorbic acid AOT/n-heptane reverse micellar system showed that the "pH" sensed by this molecule is lower than that in respective homogeneous aqueous solutions. The obtained results were rationalized taking into account three main factors (i) preferential location of ascorbic acid molecules in the interfacial region of the both types of reverse micelles; (ii) postulate that the pH of the interface is lower than that of the water pool of reverse micelles and (iii) different structure of the interface of the reverse micelles made by AOT in n-heptane and those formed by Igepal CO-520 I cyclohexane. Some possible consequences of these findings are discussed.

  6. Infusion of radionuclides throughout pregnancy

    International Nuclear Information System (INIS)

    Mountford-Lister, P.G.; Lambert, B.E.; Milner, A.C.; Kang, X.Z.

    1992-01-01

    This work is part of a long-term study to examine the cancer incidence in the offspring of mice exposed to 239 Pu or 147 Pm throughout pregnancy. The need to model the human intake scenario and the possibility of a critical period during uterine development necessitates constant availability of radionuclides throughout pregnancy. Various methods (multiple daily injections, infusion by external cannula and infusion by indwelling osmotic pump) have been examined and osmotic infusion pumps chosen. These pumps result in a near-constant blood concentration for up to 21 days. Part of the study is the estimation of dose to the critical haemopoietic tissues of the pup from a knowledge of the radionuclide distribution and kinetics. At present the distribution has been followed from birth to 180 days. Activity in the suckling pups at 7 days old is around 1 percent of the infused activity, though most of this is accounted for by the contents of the stomach and gastrointestinal tract. The liver and femur account for around 0.025 percent and 0.012 percent respectively per pup. Activity increases in both liver and femur during lactation after which both concentration and activity fall with time. Long-term studies with the pups of dams exposed to a range of 239 Pu concentrations between 0-70 kBq/kg are underway. Correlation of average organ dose with tumour incidence will be determined at completion of the life-span study. (Author) 39 refs., 5 tabs., 6 figs

  7. Flow-induced immobilization of glucose oxidase in nonionic micellar nanogels for glucose sensing.

    Science.gov (United States)

    Cardiel, Joshua J; Zhao, Ya; Tonggu, Lige; Wang, Liguo; Chung, Jae-Hyun; Shen, Amy Q

    2014-10-21

    A simple microfluidic platform was utilized to immobilize glucose oxidase (GOx) in a nonionic micellar scaffold. The immobilization of GOx was verified by using a combination of cryogenic electron microscopy (cryo-EM), scanning electron microscopy (SEM), and ultraviolet spectroscopy (UV) techniques. Chronoamperometric measurements were conducted on nanogel-GOx scaffolds under different glucose concentrations, exhibiting linear amperometric responses. Without impacting the lifetime and denaturation of GOx, the nonionic nanogel provides a favorable microenvironment for GOx in biological media. This flow-induced immobilization method in a nonionic nanogel host matrix opens up new pathways for designing a simple, fast, biocompatible, and cost-effective process to immobilize biomolecules that are averse to ionic environments.

  8. Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy

    International Nuclear Information System (INIS)

    Carvalho, Rui A.; Sousa, Rui P.B.; Cadete, Virgilio J.J.; Lopaschuk, Gary D.; Palmeira, Carlos M.M.; Bjork, James A.; Wallace, Kendall B.

    2010-01-01

    Doxorubicin (Adriamycin ® ) is a potent and broad-spectrum antineoplastic agent, the clinical utility of which is restricted by a cumulative and progressive cardiomyopathy that develops with repeated dosing. Fundamental to the cardiac failure is an interference with mitochondrial respiration and inhibition of oxidative phosphorylation. Global gene expression arrays in cardiac tissue indicate that inhibition of mitochondrial oxidative phosphorylation by doxorubicin (DOX) is accompanied by a decreased expression of genes related to aerobic fatty acid oxidation and a corresponding increase in expression of genes involved in anaerobic glycolysis, possibly as an alternate source for ATP production. The aim of this investigation was to determine whether this is also manifest at the metabonomic level as a switch in metabolic flux in cardiac tissue, and whether this can be averted by co-administering the cardioprotective drug, dexrazoxane (DZR). 13 C-isotopomer analysis of isolated perfused hearts from male Sprague-Dawley rats receiving 6 weekly s.c. injections of 2 mg/kg DOX demonstrated a shift from the preferential oxidation of fatty acids to enhanced oxidation of glucose and lactate plus pyruvate, indicative of a compensatory shift towards increased pyruvate dehydrogenase activity. Substrate-selective isotopomer analysis combined with western blots indicate an inhibition of long-chain fatty acid oxidation and not MCAD activity or fatty acyl-carnitine transport. Co-administering DZR averted many treatment-related changes in cardiac substrate metabolism, consistent with DZR being an effective cardioprotective agent against DOX-induced cardiomyopathy. This switch in substrate metabolism resembles that described for other models of cardiac failure; accordingly, this change in metabolic flux may represent a general compensatory response of cardiac tissue to imbalances in bioenergetic demand and supply, and not a characteristic unique to DOX-induced cardiac failure itself.

  9. Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice

    Energy Technology Data Exchange (ETDEWEB)

    Vijay, Vikrant; Moland, Carrie L.; Han, Tao; Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Mathematics, Korea University, Sejong (Korea, Republic of); Herman, Eugene H. [Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850-9734 (United States); Jenkins, G. Ronald [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Cummings, Connie A. [UltraPath Imaging, 2228 Page Road, Durham, NC 27703 (United States); Gao, Yuan; Cao, Zhijun; Yu, Li-Rong [Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2016-03-15

    Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F{sub 1} mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before each weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. - Highlights: • Altered mitochondria-related gene expression before heart injury by doxorubicin • Dexrazoxane mitigated doxorubicin-induced early expression changes in mitochondria. • Dexrazoxane completely ameliorated doxorubicin-induced pathology in mouse heart.

  10. p21WAF1/Cip1/Sdi1 knockout mice respond to doxorubicin with reduced cardiotoxicity

    International Nuclear Information System (INIS)

    Terrand, Jerome; Xu, Beibei; Morrissy, Steve; Dinh, Thai Nho; Williams, Stuart; Chen, Qin M.

    2011-01-01

    Doxorubicin (Dox) is an antineoplastic agent that can cause cardiomyopathy in humans and experimental animals. As an inducer of reactive oxygen species and a DNA damaging agent, Dox causes elevated expression of p21 WAF1/Cip1/Sdi1 (p21) gene. Elevated levels of p21 mRNA and p21 protein have been detected in the myocardium of mice following Dox treatment. With chronic treatment of Dox, wild type (WT) animals develop cardiomyopathy evidenced by elongated nuclei, mitochondrial swelling, myofilamental disarray, reduced cardiac output, reduced ejection fraction, reduced left ventricular contractility, and elevated expression of ANF gene. In contrast, p21 knockout (p21KO) mice did not show significant changes in the same parameters in response to Dox treatment. In an effort to understand the mechanism of the resistance against Dox induced cardiomyopathy, we measured levels of antioxidant enzymes and found that p21KO mice did not contain elevated basal or inducible levels of glutathione peroxidase and catalase. Measurements of 6 circulating cytokines indicated elevation of IL-6, IL-12, IFNγ and TNFα in Dox treated WT mice but not p21KO mice. Dox induced elevation of IL-6 mRNA was detected in the myocardium of WT mice but not p21KO mice. While the mechanism of the resistance against Dox induced cardiomyopathy remains unclear, lack of inflammatory response may contribute to the observed cardiac protection in p21KO mice. -- Highlights: ► Doxorubicin induces p21 elevation in the myocardium. ► Doxorubicin causes dilated cardiomyopathy in wild type mice. ► p21 Knockout mice are resistant against doxorubicin induced cardiomyopathy. ► Lack of inflammatory response correlates with the resistance in p21 knockout mice.

  11. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial.

    Science.gov (United States)

    Skorupski, K A; Uhl, J M; Szivek, A; Allstadt Frazier, S D; Rebhun, R B; Rodriguez, C O

    2016-03-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. © 2013 John Wiley & Sons Ltd.

  12. Modulation of DNA damage response and induction of apoptosis mediates synergism between doxorubicin and a new imidazopyridine derivative in breast and lung cancer cells.

    Science.gov (United States)

    El-Awady, Raafat A; Semreen, Mohammad H; Saber-Ayad, Maha M; Cyprian, Farhan; Menon, Varsha; Al-Tel, Taleb H

    2016-01-01

    DNA damage response machinery (DDR) is an attractive target of cancer therapy. Modulation of DDR network may alter the response of cancer cells to DNA damaging anticancer drugs such as doxorubicin. The aim of the present study is to investigate the effects of a newly developed imidazopyridine (IAZP) derivative on the DDR after induction of DNA damage in cancer cells by doxorubicin. Cytotoxicity sulphrhodamine-B assay showed a weak anti-proliferative effect of IAZP alone on six cancer cell lines (MCF7, A549, A549DOX11, HepG2, HeLa and M8) and a normal fibroblast strain. Combination of IAZP with doxorubicin resulted in synergism in lung (A549) and breast (MCF7) cancer cells but neither in the other cancer cell lines nor in normal fibroblasts. Molecular studies revealed that synergism is mediated by modulation of DNA damage response and induction of apoptosis. Using constant-field gel electrophoresis and immunofluorescence detection of γ-H2AX foci, IAZP was shown to inhibit the repair of doxorubicin-induced DNA damage in A549 and MCF7 cells. Immunoblot analysis showed that IAZP suppresses the phosphorylation of the ataxia lelangiectasia and Rad3 related (ATR) protein, which is an important player in the response of cancer cells to chemotherapy-induced DNA damage. Moreover, IAZP augmented the doxorubicin-induced degradation of p21, activation of p53, CDK2, caspase 3/7 and phosphorylation of Rb protein. These effects enhanced doxorubicin-induced apoptosis in both cell lines. Our results indicate that IAZP is a promising agent that may enhance the cytotoxic effects of doxorubicin on some cancer cells through targeting the DDR. It is a preliminary step toward the clinical application of IAZP in combination with anticancer drugs and opens the avenue for the development of compounds targeting the DDR pathway that might improve the therapeutic index of anticancer drugs and enhance their cure rate. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Design of Infusion Schemes for Neuroreceptor Imaging

    DEFF Research Database (Denmark)

    Feng, Ling; Svarer, Claus; Madsen, Karine

    2016-01-01

    for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C...... state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous...

  14. Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials

    Directory of Open Access Journals (Sweden)

    Van Arendonk Kyle J

    2011-06-01

    Full Text Available Abstract Background The emergence of multi-drug resistant Gram-negatives (MDRGNs coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion. Methods Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR and 95% confidence intervals (CI were calculated using Mantel-Haenszel random-effects models. Results Fourteen randomized controlled trials (RCTs were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37 or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06 compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws. Conclusions No clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed.

  15. Application of Fluorescence Emission for Characterization of Albendazole and Ricobendazole Micellar Systems: Elucidation of the Molecular Mechanism of Drug Solubilization Process.

    Science.gov (United States)

    Priotti, Josefina; Leonardi, Darío; Pico, Guillermo; Lamas, María C

    2018-04-01

    Albendazole (ABZ) and ricobendazole (RBZ) are referred to as class II compounds in the Biopharmaceutical Classification System. These drugs exhibit poor solubility, which profoundly affects their oral bioavailability. Micellar systems are excellent pharmaceutical tools to enhance solubilization and absorption of poorly soluble compounds. Polysorbate 80 (P80), poloxamer 407 (P407), sodium cholate (Na-C), and sodium deoxycholate (Na-DC) have been selected as surfactants to study the solubilization process of these drugs. Fluorescence emission was applied in order to obtain surfactant/fluorophore (S/F) ratio, critical micellar concentration, protection efficiency of micelles, and thermodynamic parameters. Systems were characterized by their size and zeta potential. A blue shift from 350 to 345 nm was observed when ABZ was included in P80, Na-DC, and Na-C micelles, while RBZ showed a slight change in the fluorescence band. P80 showed a significant solubilization capacity: S/F values were 688 for ABZ at pH 4 and 656 for RBZ at pH 6. Additionally, P80 micellar systems presented the smallest size (10 nm) and their size was not affected by pH change. S/F ratio for bile salts was tenfold higher than for the other surfactants. Quenching plots were linear and their constant values (2.17/M for ABZ and 2.29/M for RBZ) decreased with the addition of the surfactants, indicating a protective effect of the micelles. Na-DC showed better protective efficacy for ABZ and RBZ than the other surfactants (constant values 0.54 and 1.57/M, respectively), showing the drug inclusion into the micelles. Entropic parameters were negative in agreement with micelle formation.

  16. Intravenous lidocaine infusion--a new treatment of chronic painful diabetic neuropathy?

    DEFF Research Database (Denmark)

    Kastrup, J; Petersen, P; Dejgård, A

    1987-01-01

    after lidocaine infusion compared to after saline infusion (P less than 0.05 and P less than 0.02, respectively). The duration of the individual effect ranged from 3 to 21 days. Lidocaine infusion had no effect on the objective measurements of neuropathy. Intravenous lidocaine infusion seems to be a new...

  17. Epstein-Barr virus EBNA2 directs doxorubicin resistance of B cell lymphoma through CCL3 and CCL4-mediated activation of NF-κB and Btk.

    Science.gov (United States)

    Kim, Joo Hyun; Kim, Won Seog; Hong, Jung Yong; Ryu, Kung Ju; Kim, Seok Jin; Park, Chaehwa

    2017-01-17

    Epstein-Barr virus (EBV)-encoded nuclear antigen, EBNA2, expressed in EBV-infected B lymphocytes is critical for lymphoblastoid cell growth. Microarray profiling and cytokine array screening revealed that EBNA2 is associated with upregulation of the chemokines CCL3 and CCL4 in lymphoma cells. Depletion or inactivation of CCL3 or CCL4 sensitized DLBCL cells to doxorubicin. Our results indicate that EBV influences cell survival via an autocrine mechanism whereby EBNA2 increases CCL3 and CCL4, which in turn activate the Btk and NF-κB pathways, contributing to doxorubicin resistance of B lymphoma cells. Western blot data further confirmed that CCL3 and CCL4 direct activation of Btk and NF-κB. Based on these findings, we propose that a pathway involving EBNA2/Btk/NF-κB/CCL3/CCL4 plays a key role in doxorubicin resistance, and therefore, inhibition of specific components of this pathway may sensitize lymphoma cells to doxorubicin. Evaluation of the relationship between CCL3 expression and EBV infection revealed high CCL3 levels in EBV-positive patients. Our data collectively suggest that doxorubicin treatment for EBNA2-positive DLBCL cells may be effectively complemented with a NF-κB or Btk inhibitor. Moreover, evaluation of the CCL3 and CCL4 levels may be helpful for selecting DLBCL patients likely to benefit from doxorubicin treatment in combination with the velcade or ibrutinib.

  18. MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrea Turner

    Full Text Available The Map kinase Activating Death Domain containing protein (MADD isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.

  19. Targeting thyroid cancer with acid-triggered release of doxorubicin from silicon dioxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Li SJ

    2017-08-01

    Full Text Available Shijie Li,1 Daqi Zhang,1 Shihou Sheng,2 Hui Sun1 1Department of Thyroid Surgery, 2Department of Gastrointestinal Colorectal and Anal Surgery, China–Japan Union Hospital of Jilin University, Chang Chun, People’s Republic of China Abstract: Currently, therapy for thyroid cancer mainly involves surgery and radioiodine therapy. However, chemotherapy can be used in advanced and aggressive thyroid cancer that cannot be treated by other options. Nevertheless, a major obstacle to the successful treatment of thyroid cancer is the delivery of drugs to the thyroid gland. Here, we present an example of the construction of silicon dioxide nanoparticles with thyroid–stimulating-hormone receptor-targeting ligand that can specifically target the thyroid cancer. Doxorubicin nanoparticles can be triggered by acid to release the drug payload for cancer therapy. These nanoparticles shrink the tumor size in vivo with less toxic side effects. This research paves the way toward effective chemotherapy for thyroid cancer. Keywords: thyroid cancer, silicon dioxide nanoparticle, doxorubicin, acid-triggered release

  20. Doxorubicin Loaded Chitosan-W18 O49 Hybrid Nanoparticles for Combined Photothermal-Chemotherapy.

    Science.gov (United States)

    Yuan, Shanmei; Hua, Jisong; Zhou, Yinyin; Ding, Yin; Hu, Yong

    2017-08-01

    Combined treatment is more effective than single treatment against most forms of cancer. In this work, doxorubicin loaded chitosan-W 18 O 49 nanoparticles combined with the photothermal therapy and chemotherapy are fabricated through the electrostatic interaction between positively charged chitosan and negatively charged W 18 O 49 nanoparticles. The in vitro and in vivo behaviors of these nanoparticles are examined by dynamic light scattering, transmission electron microscopy, cytotoxicity, near-infrared fluorescence imaging, and tumor growth inhibition experiment. These nanoparticles have a mean size around 110 nm and show a pH sensitive drug release behavior. After irradiation by the 980 nm laser, these nanoparticles show more pronounced cytotoxicity against HeLa cells than that of free doxorubicin or photothermal therapy alone. The in vivo experiments confirm that their antitumor ability is significantly improved, resulting in superior efficiency in impeding tumor growth and extension of the lifetime of mice. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Forearm metabolism during infusion of adrenaline

    DEFF Research Database (Denmark)

    Simonsen, L; Stefl, B; Bülow, J

    2000-01-01

    Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were...... catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured...... by the local 133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a-v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0.3 nmol kg-1 min-1. No difference in the metabolic information obtained in the fasting...

  2. ArtsIN: Arts Integration and Infusion Framework

    Science.gov (United States)

    Hartle, Lynn C.; Pinciotti, Patricia; Gorton, Rebecca L.

    2015-01-01

    Teaching to meet the diverse learning needs of twenty-first century, global learners can be challenging, yet a growing body of research points to the proved successes of arts-infused and integrated curricula, especially for building capacity for learning and motivation. This article presents the ArtsIN: Arts Integration and Infusion framework, a…

  3. An integrated assessment of morphology, size, and complement activation of the PEGylated liposomal doxorubicin products Doxil®, Caelyx®, DOXOrubicin, and SinaDoxosome

    DEFF Research Database (Denmark)

    Wibroe, Peter P; Ahmadvand, Davoud; Oghabian, Mohammad Ali

    2016-01-01

    follow-on products DOXOrubicin (approved by the US Food and Drug Administration) and SinaDoxosome (produced in Iran) by cryogenic transmission electron microscopy, dynamic light scattering and Nanoparticle Tracking Analysis, and assess their potential in activating the complement system in human sera. We...... found subtle physicochemical differences between the tested liposomal products and even between the tested batches of Doxil® and Caelyx®. Notably, these included differences in vesicular population aspect ratios and particle number. Among the tested products, only SinaDoxosome, in addition...

  4. Bupivacaine constant continuous surgical wound infusion versus continuous epidural infusion for post cesarean section pain, randomized placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Hossam A. ELShamaa

    2016-10-01

    Conclusion: The current study demonstrated that bupivacaine administered by continuous epidural infusion provided a significantly lower pain scores with mobilization, and hence better analgesia for post cesarean section pain in the first postoperative day compared to continuous bupivacaine wound infusion through fenestrated catheter using the constant flow PainFusor system.

  5. Doxorubicin conjugation and drug linker chemistry alter the intravenous and pulmonary pharmacokinetics of a PEGylated Generation 4 polylysine dendrimer in rats.

    Science.gov (United States)

    Leong, Nathania J; Mehta, Dharmini; McLeod, Victoria M; Kelly, Brian D; Pathak, Rashmi; Owen, David J; Porter, Christopher Jh; Kaminskas, Lisa M

    2018-05-28

    PEGylated polylysine dendrimers have demonstrated potential as inhalable drug delivery systems that can improve the treatment of lung cancers. Their treatment potential may be enhanced by developing constructs that display prolonged lung retention, together with good systemic absorption, the capacity to passively target lung tumours from the blood and highly selective, yet rapid liberation in the tumour microenvironment. This study sought to characterise how the nature of cathepsin B cleavable peptide linkers, used to conjugate doxorubicin to a PEGylated (PEG570) G4 polylysine dendrimer, affect drug liberation kinetics and intravenous and pulmonary pharmacokinetics in rats. The construct bearing a self-emolative diglycolic acid-V-Citrulline linker exhibited faster doxorubicin release kinetics compared to constructs bearing self emolative diglycolic acid-GLFG, or non-self emolative glutaric acid-GLFG linkers. The V-Citrulline construct exhibited slower plasma clearance, but faster absorption from the lungs than a GLFG construct, although mucociliary clearance and urinary elimination were unchanged. Doxorubicin-conjugation enhanced localisation in the bronchoalveolar lavage fluid compared to lung tissue, suggesting that projection of doxorubicin from the dendrimer surface reduced tissue uptake. These data show that the linker chemistry employed to conjugate drugs to PEGylated carriers can affect drug release profiles and systemic and lung disposition. Copyright © 2018. Published by Elsevier Inc.

  6. Delivery interaction between co-infused medications: an in vitro modeling study of microinfusion.

    Science.gov (United States)

    Tsao, Amy C; Lovich, Mark A; Parker, Michael J; Zheng, Hui; Peterfreund, Robert A

    2013-01-01

    To test the hypothesis that steady-state drug delivery by continuous infusion is predictably affected by a second drug infusion in the same lumen. Clinicians commonly administer two drugs by continuous infusion through one central venous catheter lumen (co-infusion). To limit fluid delivery, low flow rate carriers transport concentrated drug solutions; a method called microinfusion. How microinfusion delivery of one drug is affected by a second drug infusion has not been explored. Two water-soluble dyes, tartrazine and erioglaucine, infused at 3 ml · h(-1), modeled drug delivery through a four stopcock linear manifold and catheter lumen. A pump drove a carrier fluid (10 ml · h(-1)). After tartrazine reached steady-state delivery, erioglaucine entered downstream or upstream of the tartrazine infusion. Quantitative spectrophotometry measured dye delivery. Starting erioglaucine's infusion upstream of tartrazine's entry caused a transient tartrazine bolus (duration 10 min, peak drug delivery 20% higher than target levels). Starting erioglaucine's infusion downstream produced a similar amplitude, briefer, bolus. Stopping the erioglaucine infusion caused a transient reduction in tartrazine delivery. Measured delivery profiles were comparable to prediction models. We confirmed the hypothesis that delivery of one infused drug is transiently affected by starting or stopping a second drug infusion in the same line. The magnitude of the changes can be estimated quantitatively. The clinical impact depends on the drugs being co-infused and patient sensitivity, but could be clinically important; the findings have safety implications for infused medication delivery to critically ill or anesthetized children. We recommend minimizing infusion system dead volumes, connecting the most essential infusion(s) to the main fluid pathway as close as possible to the patient, and recognizing the potential for unintended alterations in delivery when multiple drugs co-infuse. © 2012

  7. Maximizing the Benefit-Cost Ratio of Anthracyclines in Metastatic Breast Cancer: Case Report of a Patient with a Complete Response to High-Dose Doxorubicin

    Directory of Open Access Journals (Sweden)

    Kevin Shee

    2016-12-01

    Full Text Available Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2– mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months. The patient was treated with the cardioprotective agent dexrazoxane, and changes in cardiac markers [e.g. decreases in ejection fraction (EF] were immediately addressed by therapeutic intervention with the ACE inhibitor lisinopril and beta-blocker metoprolol. The patient had a complete response to doxorubicin therapy, with a cumulative dose of 1,350 mg/m2, which is significantly above the recommended limits, and to our knowledge, the highest dose reported in literature. Two and a half years after the last doxorubicin cycle, the patient is asymptomatic with no cardiotoxicity and an excellent quality of life. This case highlights the importance of careful monitoring and management of doxorubicin-mediated cardiotoxicity, and that higher cumulative doses of anthracyclines can be considered in patients with ongoing clinical benefit.

  8. Continuous infusion of chemotherapy: focus on 5-fluorouracil and fluorodeoxyuridine

    NARCIS (Netherlands)

    Poorter, R. L.; Bakker, P. J.; Veenhof, C. H.

    1998-01-01

    Continuous infusion of chemotherapy is one of the developments to try to improve the treatment of metastatic cancer. There is a sound theoretical rationale to deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of reliable venous access devices and portable infusion pumps

  9. Safe and tolerable one-hour pamidronate infusion for multiple myeloma patients

    Directory of Open Access Journals (Sweden)

    Dimitrios Chantzichristos

    2008-09-01

    Full Text Available Dimitrios Chantzichristos, Andréasson Björn, Johansson PeterDepartment of Internal Medicine, Uddevalla Hospital, Uddevalla, SwedenBackground: Once a month, patients with multiple myeloma received an infusion of bisphosphonates, principally to reduce osteoclastic bone resorption. Recommended infusion time for pamidronate is 2 hours in the US and 4 hours in Europe because of its potential nephrotoxicity. From 2003, a 90 mg infusion of pamidronate was provided over 1 hour to patients with no pre-existing renal impairment, in the Daily Care Unit at Uddevalla Hospital.Method: Retrospective analysis of the renal deterioration, serum calcium, and adverse effects in patients with multiple myeloma treated with 1-hour pamidronate 90 mg infusion from January 2003 to April 2007.Results: Seventy-nine patients provided valuable data. A total number of 846 infusions were given and the median number of infusion to each patient was 11. Significant creatinine elevation was seen in 7 patients (8.9%, after 19 infusions (2.2%. Renal deterioration occurred in 5 of these 7 patients, which was related to progress of the myeloma or opportunistic infections. Prevalence of infusion-related events was 0.8% and the mean total S-Ca was 0.05 mmol/L lower than the baseline.Conclusion: Few events of renal deterioration, hypocalcemia, or other adverse effects resulted from a 1-hour pamidronate 90 mg infusion for multiple myeloma patients with no pre-existing renal impairment.Keywords: bisphosphonates, pamidronate, multiple myeloma, infusion time

  10. Septal co-infusions of glucose with the benzodiazepine agonist chlordiazepoxide impair memory, but co-infusions of glucose with the opiate morphine do not.

    Science.gov (United States)

    Krebs-Kraft, Desiree L; Parent, Marise B

    2010-03-30

    We have found repeatedly that medial septal (MS) infusions of glucose impair memory when co-infused with the gamma-amino butyric acid (GABA) agonist muscimol. The present experiments sought to determine whether the memory-impairing effects of this concentration of glucose would generalize to another GABA(A) receptor agonist and to an agonist from another neurotransmitter system that is known to impair memory. Specifically, we determined whether the dose of glucose that produces memory deficits when combined with muscimol in the MS would also impair memory when co-infused with the GABA(A) receptor modulator chlordiazepoxide (CDP) or the opiate morphine. Male Sprague-Dawley rats were given MS co-infusions and then 15 min later tested for spontaneous alternation or given shock avoidance training (retention tested 48 h later). The results showed that MS infusions of the higher dose of glucose with morphine did not produce memory deficits, whereas, the performance of rats given MS co-infusions of CDP with glucose was impaired. These findings suggest that the memory-impairing effects of brain glucose administration may involve an interaction with the GABA(A) receptor. (c) 2009 Elsevier Inc. All rights reserved.

  11. 75 FR 21641 - Infusion Pumps; Public Meeting; Request for Comments

    Science.gov (United States)

    2010-04-26

    ...] Infusion Pumps; Public Meeting; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION... announcing a public meeting regarding external infusion pumps. The purpose of the meeting is to inform the public about current problems associated with external infusion pump use, to help the agency identify...

  12. Solvation dynamics in triton-X-100 and triton-X-165 micelles: Effect of micellar size and hydration

    Science.gov (United States)

    Kumbhakar, Manoj; Nath, Sukhendu; Mukherjee, Tulsi; Pal, Haridas

    2004-09-01

    Dynamic Stokes' shift measurements using coumarin 153 as the fluorescence probe have been carried out to study solvation dynamics in two nonionic micelles, viz., triton-X-100 (TX-100) and triton-X-165 (TX-165). In both the micelles, the solvent relaxation dynamics is biexponential in nature. While the fast solvation time τs1 is seen to be almost similar for both the micelles, the slow solvation time τs2 is found to be appreciably smaller in TX-165 than in TX-100 micelle. Dynamic light scattering measurements indicate that the TX-165 micelles are substantially smaller in size than that of TX-100. Assuming similar core size for both the micelles, as expected from the similar chemical structures of the nonpolar ends for both the surfactants, the Palisade layer is also indicated to be substantially thinner for TX-165 micelles than that of TX-100. The aggregation number of TX-165 micelles is also found to be substantially smaller than that of TX-100 micelles. Fluorescence spectral studies of C153 dye in the two micelles indicate that the Palisade layer of TX-165 micelles is more polar than that of TX-100 micelles. Fluorescence anisotropy measurements indicate that the microviscosity in the Palisade layer of TX-165 micelles is also lower than that of TX-100 micelles. Based on these results it is inferred that the structure of the Palisade layer of TX-165 micelles is quite loose and have higher degree hydration in comparison to that of TX-100 micelles. Due to these structural differences in the Palisade layers of TX-165 and TX-100 micelles the solvation dynamics is faster in the former micelles than in the latter. It has been further inferred that in the present systems the collective response of the water molecules at somewhat away from the probes is responsible for the faster component of the solvation time, which does not reflect much of the structural changes of the micellar Palisade layer. On the contrary, the slower solvation time component, which is mainly due to

  13. Using higher doses to compensate for tubing residuals in extended-infusion piperacillin-tazobactam.

    Science.gov (United States)

    Lam, Wendy J; Bhowmick, Tanaya; Gross, Alan; Vanschooneveld, Trevor C; Weinstein, Melvin P

    2013-06-01

    To mathematically assess drug losses due to infusion line residuals and evaluate methods to compensate for drug loss due to residual volumes in intravenous pump tubing. Literature was accessed through Ovid MEDLINE (1996-February 2013), using combinations of the search terms tubing residuals, residual volume, residual medication, intravenous infusions, intravenous injections, piperacillin, piperacillin-tazobactam, β-lactams, equipment design, infusion pumps, extended infusion, extended administration, and prolonged infusion. In addition, select reference citations from publications identified were reviewed. All articles that involved extended-infusion piperacillin-tazobactam implementation strategies were included in the review. Infusion pump characteristics and tubing residuals can affect extended-infusion piperacillin-tazobactam dosing strategies. Two studies addressing tubing residuals were identified. Both studies recommended increasing infusion volumes to compensate for tubing residuals. One study also recommended decreasing infusion-line dead space by using alternative infusion pump systems. Study calculations suggest that higher doses of piperacillin-tazobactam may be used to account for medication left in tubing residuals if alternative infusion pump systems cannot be obtained, and increased infusion volumes are not an option. Extended-infusion piperacillin-tazobactam has been used as a method of maximizing pharmacodynamic target attainment. Use of higher doses of piperacillin-tazobactam may be a reasonable method to compensate for drug loss due to residual volumes in large-bore intravenous pump tubing.

  14. Amplification of Chirality through Self-Replication of Micellar Aggregates in Water

    KAUST Repository

    Bukhriakov, Konstantin

    2015-03-17

    We describe a system in which the self-replication of micellar aggregates results in a spontaneous amplification of chirality in the reaction products. In this system, amphiphiles are synthesized from two "clickable" fragments: a water-soluble "head" and a hydrophobic "tail". Under biphasic conditions, the reaction is autocatalytic, as aggregates facilitate the transfer of hydrophobic molecules to the aqueous phase. When chiral, partially enantioenriched surfactant heads are used, a strong nonlinear induction of chirality in the reaction products is observed. Preseeding the reaction mixture with an amphiphile of one chirality results in the amplification of this product and therefore information transfer between generations of self-replicating aggregates. Because our amphiphiles are capable of catalysis, information transfer, and self-assembly into bounded structures, they present a plausible model for prenucleic acid "lipid world" entities. © 2015 American Chemical Society.

  15. Smart release of doxorubicin loaded on polyetheretherketone (PEEK) surface with 3D porous structure.

    Science.gov (United States)

    Ouyang, Liping; Sun, Zhenjie; Wang, Donghui; Qiao, Yuqin; Zhu, Hongqin; Ma, Xiaohan; Liu, Xuanyong

    2018-03-01

    It is important to fabricate an implant possessing environment sensitive drug delivery. In this work, the construction of 3D porous structure on polyetheretherketone (PEEK) surface and pH sensitive polymer, chitosan, was introduced. The smart release of doxorubicin can be realized on the 3D porous surface of PEEK loading chitosan. We give a feasible explanation for the effect of chitosan on smart drug release according to Henderson-Hasselbalch equation. Furthermore, the intracellular drug content of the cell cultured on the samples with highest chitosan is significantly higher at pH 4.0, whereas lower at pH 7.4 than other samples. The smart release of doxorubicin via modification with chitosan onto 3D porous PEEK surface paves the way for the application of PEEK in drug loading platform for recovering bone defect caused by malignant bone tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Superselective intraarterial infusion therapy for head and neck carcinomas

    International Nuclear Information System (INIS)

    Nakatani, Hiroaki; Sawada, Shoichi; Takeda, Taizo

    2004-01-01

    We report the results of superselective intraarterial cisplatin (CDDP) infusion therapy combined with irradiation for 23 patients, mainly advanced head and neck carcinoma. All patients received intraarterial CDDP infusions with intravenous sodium thiosulfate (STS) neutralization. CDDP infusion was performed by the Seldinger's technique in 16 patients and by the implanted intraarterial reservoir system in 7 patients. STS was also infused by the reservoir system implanted at the forearm in most patients. An overall response was observed in 21 of the 23 (91.3%) patients. Complete and partial responses were achieved in 16 (69.6%) and 5 (21.7%) patients, respectively. There were no patients with worse than grade III complications. We concluded that superselective intraarterial infusion therapy with a high dose of CDDP and STS was very effective for the management of advanced head and neck carcinomas and we recommend the implantable reservoir system for both CDDP and STS administration as an easy and low-invasive method. (author)

  17. Infusion pressure and pain during microneedle injection into skin of human subjects

    Science.gov (United States)

    Gupta, Jyoti; Park, Sohyun; Bondy, Brian; Felner, Eric I.; Prausnitz, Mark R.

    2011-01-01

    Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures cause more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. PMID:21684001

  18. Associations between bolus infusion of hydrocortisone, glycemic variability and insulin infusion rate variability in critically Ill patients under moderate glycemic control

    NARCIS (Netherlands)

    van Hooijdonk, Roosmarijn T. M.; Binnekade, Jan M.; Bos, Lieuwe D. J.; Horn, Janneke; Juffermans, Nicole P.; Abu-Hanna, Ameen; Schultz, Marcus J.

    2015-01-01

    We retrospectively studied associations between bolus infusion of hydrocortisone and variability of the blood glucose level and changes in insulin rates in intensive care unit (ICU) patients. 'Glycemic variability' and 'insulin infusion rate variability' were calculated from and expressed as the

  19. The fabrication of highly ordered block copolymer micellar arrays: control of the separation distances of silicon oxide dots

    Science.gov (United States)

    Yoo, Hana; Park, Soojin

    2010-06-01

    We demonstrate the fabrication of highly ordered silicon oxide dotted arrays prepared from polydimethylsiloxane (PDMS) filled nanoporous block copolymer (BCP) films and the preparation of nanoporous, flexible Teflon or polyimide films. Polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) films were annealed in toluene vapor to enhance the lateral order of micellar arrays and were subsequently immersed in alcohol to produce nano-sized pores, which can be used as templates for filling a thin layer of PDMS. When a thin layer of PDMS was spin-coated onto nanoporous BCP films and thermally annealed at a certain temperature, the PDMS was drawn into the pores by capillary action. PDMS filled BCP templates were exposed to oxygen plasma environments in order to fabricate silicon oxide dotted arrays. By addition of PS homopolymer to PS-b-P2VP copolymer, the separation distances of micellar arrays were tuned. As-prepared silicon oxide dotted arrays were used as a hard master for fabricating nanoporous Teflon or polyimide films by spin-coating polymer precursor solutions onto silicon patterns and peeling off. This simple process enables us to fabricate highly ordered nanoporous BCP templates, silicon oxide dots, and flexible nanoporous polymer patterns with feature size of sub-20 nm over 5 cm × 5 cm.

  20. The fabrication of highly ordered block copolymer micellar arrays: control of the separation distances of silicon oxide dots

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hana; Park, Soojin, E-mail: spark@unist.ac.kr [Interdisciplinary School of Green Energy, Ulsan National Institute of Science and Technology, Banyeon-ri 100, Ulsan 689-798 (Korea, Republic of)

    2010-06-18

    We demonstrate the fabrication of highly ordered silicon oxide dotted arrays prepared from polydimethylsiloxane (PDMS) filled nanoporous block copolymer (BCP) films and the preparation of nanoporous, flexible Teflon or polyimide films. Polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) films were annealed in toluene vapor to enhance the lateral order of micellar arrays and were subsequently immersed in alcohol to produce nano-sized pores, which can be used as templates for filling a thin layer of PDMS. When a thin layer of PDMS was spin-coated onto nanoporous BCP films and thermally annealed at a certain temperature, the PDMS was drawn into the pores by capillary action. PDMS filled BCP templates were exposed to oxygen plasma environments in order to fabricate silicon oxide dotted arrays. By addition of PS homopolymer to PS-b-P2VP copolymer, the separation distances of micellar arrays were tuned. As-prepared silicon oxide dotted arrays were used as a hard master for fabricating nanoporous Teflon or polyimide films by spin-coating polymer precursor solutions onto silicon patterns and peeling off. This simple process enables us to fabricate highly ordered nanoporous BCP templates, silicon oxide dots, and flexible nanoporous polymer patterns with feature size of sub-20 nm over 5 cm x 5 cm.

  1. Prepreg and infusion processes for modern wind turbine blades

    Energy Technology Data Exchange (ETDEWEB)

    Shennan, C. [Hexcel, Cambridge (United Kingdom)

    2013-09-01

    The different elements of wind turbine blades have been analyzed for their main function, performance requirements and drivers. Key drivers can be simplified to either performance or cost. The use of prepreg and infusion to make these blade elements has then been compared and shows, from a comparison of test laminates, that prepreg typically delivers higher mechanical performance on both glass and carbon. One of the main process differences, cure temperature, has been overcome with the introduction of M79 which cures at 70 deg. - 80 deg. C. M79 combines this low cure temperature with a much lower reaction enthalpy allowing shorter cure cycles. This means that prepregs can now be cured in the same molds, at the same temperatures and with the same foam as used in a conventional infusion process. Although prepreg and infusion are usually used separately for making blade elements, they may also be used in combination: co-infused and co-cured using prepregs for the hard to infuse unidirectional load-carrying elements and infusion for the other elements. This can thus simplify the production process. The conclusion is that unidirectional prepregs are ideally suited for the performance driven parts of the blade such as in load carrying elements. (Author)

  2. p21{sup WAF1/Cip1/Sdi1} knockout mice respond to doxorubicin with reduced cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Terrand, Jerome; Xu, Beibei; Morrissy, Steve; Dinh, Thai Nho [Department of Pharmacology,College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States); Williams, Stuart [Biomedical Engineering Program, College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States); Chen, Qin M., E-mail: qchen@email.arizona.edu [Department of Pharmacology,College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States)

    2011-11-15

    Doxorubicin (Dox) is an antineoplastic agent that can cause cardiomyopathy in humans and experimental animals. As an inducer of reactive oxygen species and a DNA damaging agent, Dox causes elevated expression of p21{sup WAF1/Cip1/Sdi1} (p21) gene. Elevated levels of p21 mRNA and p21 protein have been detected in the myocardium of mice following Dox treatment. With chronic treatment of Dox, wild type (WT) animals develop cardiomyopathy evidenced by elongated nuclei, mitochondrial swelling, myofilamental disarray, reduced cardiac output, reduced ejection fraction, reduced left ventricular contractility, and elevated expression of ANF gene. In contrast, p21 knockout (p21KO) mice did not show significant changes in the same parameters in response to Dox treatment. In an effort to understand the mechanism of the resistance against Dox induced cardiomyopathy, we measured levels of antioxidant enzymes and found that p21KO mice did not contain elevated basal or inducible levels of glutathione peroxidase and catalase. Measurements of 6 circulating cytokines indicated elevation of IL-6, IL-12, IFN{gamma} and TNF{alpha} in Dox treated WT mice but not p21KO mice. Dox induced elevation of IL-6 mRNA was detected in the myocardium of WT mice but not p21KO mice. While the mechanism of the resistance against Dox induced cardiomyopathy remains unclear, lack of inflammatory response may contribute to the observed cardiac protection in p21KO mice. -- Highlights: Black-Right-Pointing-Pointer Doxorubicin induces p21 elevation in the myocardium. Black-Right-Pointing-Pointer Doxorubicin causes dilated cardiomyopathy in wild type mice. Black-Right-Pointing-Pointer p21 Knockout mice are resistant against doxorubicin induced cardiomyopathy. Black-Right-Pointing-Pointer Lack of inflammatory response correlates with the resistance in p21 knockout mice.

  3. Use of propofol infusion in alcohol withdrawal-induced refractory delirium tremens

    DEFF Research Database (Denmark)

    Lorentzen, Kristian; Lauritsen, Anne Øberg; Bendtsen, Asger Ole

    2014-01-01

    in case reports. We aimed to evaluate the treatment of delirium tremens with propofol infusion for 48 h. MATERIAL AND METHODS: This study was a single-centre retrospective cohort analysis of 15 patient journals covering the period from May 2012 to September 2013. RESULTS: Five women and ten men were...... and mechanically ventilated in the intensive care unit. The mean propofol infusion rate was 4.22 mg/kg/h. Thirteen patients received supplemental infusion of opioids, whereas seven required concomitant vasopressor infusion. Once propofol infusion was discontinued after 48 h, 12 patients had a long awakening...

  4. Advancing medication infusion safety through the clinical integration of technology.

    Science.gov (United States)

    Gerhart, Donald; O'Shea, Kristen; Muller, Sharon

    2013-01-01

    Adverse drug events resulting from errors in prescribing or administering medications are preventable. Within a hospital system, numerous technologies are employed to address the common sources of medication error, including the use of electronic medical records, physician order entry, smart infusion pumps, and barcode medication administration systems. Infusion safety is inherently risky because of the high-risk medications administered and the lack of integration among the stand-alone systems in most institutions. Intravenous clinical integration (IVCI) is a technology that connects electronic medical records, physician order entry, smart infusion pumps, and barcode medication administration systems. It combines the safety features of an automatically programmed infusion pump (drug, concentration, infusion rate, and patient weight, all auto-programmed into the device) with software that provides visibility to real-time clinical infusion data. Our article describes the characteristics of IVCI at WellSpan Health and its impact on patient safety. The integrated infusion system has the capability of reducing medication errors, improving patient care, reducing in-facility costs, and supporting asset management. It can enhance continuous quality improvement efforts and efficiency of clinical work flow. After implementing IVCI, the institution realized a safer patient environment and a more streamlined work flow for pharmacy and nursing.

  5. GSH-targeted nanosponges increase doxorubicin-induced toxicity "in vitro" and "in vivo" in cancer cells with high antioxidant defenses.

    Science.gov (United States)

    Daga, Martina; Ullio, Chiara; Argenziano, Monica; Dianzani, Chiara; Cavalli, Roberta; Trotta, Francesco; Ferretti, Carlo; Zara, Gian Paolo; Gigliotti, Casimiro L; Ciamporcero, Eric S; Pettazzoni, Piergiorgio; Corti, Denise; Pizzimenti, Stefania; Barrera, Giuseppina

    2016-08-01

    Several reports indicate that chemo-resistant cancer cells become highly adapted to intrinsic oxidative stress by up-regulating their antioxidant systems, which causes an increase of intracellular GSH content. Doxorubicin is one of the most widely used drugs for tumor treatment, able to kill cancer cells through several mechanisms. However, doxorubicin use is limited by its toxicity and cancer resistance. Therefore, new therapeutic strategies able to reduce doses and to overcome chemo-resistance are needed. A new class of glutathione-responsive cyclodextrin nanosponges (GSH-NS), is able to release anticancer drugs preferentially in cells having high GSH content. Doxorubicin-loaded GSH-NS, in the cancer cells with high GSH content, inhibited clonogenic growth, cell viability, topoisomerase II activity and induced DNA damage with higher effectiveness than free drug. Moreover, GSH-NS reduced the development of human tumor in xenograft models more than free drug. These characteristics indicate that GSH-NS can be a suitable drug delivery carrier for future applications in cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. On–off switch-controlled doxorubicin release from thermo- and pH-responsive coated bimagnetic nanocarriers

    Energy Technology Data Exchange (ETDEWEB)

    Hammad, Mohaned; Nica, Valentin; Hempelmann, Rolf, E-mail: r.hempelmann@mx.uni-saarland.de [Saarland University, Department of Physical Chemistry (Germany)

    2016-08-15

    A switch-controlled drug release system is designed by coating of core/shell bimagnetic nanoparticles with a pH- and thermo-responsive polymer shell, which can be used as hyperthermic agent, drug carrier, and for controlled release. Doxorubicin is loaded onto the surface of the last coating layer, and a high loading efficiency of 90.5 % is obtained. The nanocarriers are characterized by FTIR, dynamic light scattering, Zeta potential, TEM, In vitro hyperthermia, and vibrating sample magnetometry. The core/shell magnetic nanoparticles (Zn{sub 0.4}Co{sub 0.6}Fe{sub 2}O{sub 4}@Zn{sub 0.4}Mn{sub 0.6}Fe{sub 2}O{sub 4}) exhibit a superparamagnetic behavior with a saturation magnetization around 45.6 emu/g and a high specific absorption rate of up to 360 W/g. The in vitro drug release experiments confirm that only a small amount of doxorubicin is released at body temperature and physiological pH, whereas a high drug release is obtained at acidic tumor pH under hyperthermia conditions (43 °C). The functionalized core/shell bimagnetic nanocarriers facilitate controllable release of doxorubicin as an effect of induced thermo- and pH-responsiveness of the polymer when are subjected to a high-frequency alternating magnetic field at acidic pH; thereby the drug release rate is controlled using on–off cycles of the applied field.Graphical Abstract.

  7. Simultaneous Determination of Tizanidine, Nimesulide, Aceclofenac and Paracetamol in Tablets and Biological Fluids Using Micellar Liquid Chromatography.

    Science.gov (United States)

    Belal, Fathalla; Omar, Mahmoud A; Derayea, Sayed; Hammad, Mohamed A; Zayed, Sahar; Saleh, Safaa F

    2018-03-01

    A simple, sensitive and rapid micellar liquid chromatographic method was developed and validated for simultaneous determination of four drugs, namely, paracetamol (PAR), tizanidine (TZD), aceclofenac (ACF) and nimesulide (NMD). Good chromatographic separation was achieved using Cyano column and micellar mobile phase consisting of 120 mM sodium dodecyl sulfate, 25 mM phosphate buffer and 10% (V/V) butanol. The pH was adjusted to three using phosphoric acid. The total retention time was below 10 min. The analysis was performed at a flow rate of 1 mL/min and a column temperature of 40°C with direct UV detection at 230 nm. Diclofenac sodium was used as the internal standard. The proposed method was validated according to the ICH guidelines and was successfully applied to the analysis of these drugs in their tablet dosage forms with high accuracy. Limits of detection were found to be 0.03, 0.07, 0.033 and 0.11 μg/mL for PAR, ACF, TZD and NMD, respectively. The high sensitivity of developed method permitted its application to the in-vitro determination of the cited drugs in spiked human plasma and urine samples, and the obtained results were satisfactory. However, PAR could not be determined in spiked human urine because its peak overlapped with that of the urine peak.

  8. Stabilization Improves Theranostic Properties of Lipiodol{sup ®}-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model

    Energy Technology Data Exchange (ETDEWEB)

    Deschamps, F., E-mail: frederic.deschamps@gustaveroussy.fr; Farouil, G. [Université Paris-Saclay, Département de radiologie Interventionnelle, Gustave Roussy (France); Gonzalez, W.; Robic, C. [Guerbet France, Guerbet (France); Paci, A.; Mir, L. M. [Université Paris-Saclay, UMR 8203 (France); Tselikas, L.; Baère, T. de [Université Paris-Saclay, Département de radiologie Interventionnelle, Gustave Roussy (France)

    2017-06-15

    PurposeTo demonstrate that stability is a crucial parameter for theranostic properties of Lipiodol{sup ®}-based emulsions during liver trans-arterial chemo-embolization.Materials and MethodsWe compared the theranostic properties of two emulsions made of Lipiodol{sup ®} and doxorubicin in two successive animal experiments (One VX2 tumour implanted in the left liver lobe of 30 rabbits). Emulsion-1 reproduced one of the most common way of preparation (ratio of oil/water: 1/1), and emulsion-2 was designed to obtain a water-in-oil emulsion with enhanced stability (ratio of oil/water: 3/1, plus an emulsifier). The first animal experiment compared the tumour selectivity of the two emulsions: seven rabbits received left hepatic arterial infusion (HAI) of emulsion-1 and eight received HAI of emulsion-2. 3D-CBCT acquisitions were acquired after HAI of every 0.1 mL to measure the densities’ ratios between the tumours and the left liver lobes. The second animal experiment compared the plasmatic and tumour doxorubicin concentrations after HAI of 1.5 mg of doxorubicin administered either alone (n = 3) or in emulsion-1 (n = 6) or in emulsion-2 (n = 6).ResultsEmulsion-2 resulted in densities’ ratios between the tumours and the left liver lobes that were significantly higher compared to emulsion-1 (up to 0.4 mL infused). Plasmatic doxorubicin concentrations (at 5 min) were significantly lower after HAI of emulsion-2 (19.0 μg/L) than emulsion-1 (275.3 μg/L, p < 0.01) and doxorubicin alone (412.0 μg/L, p < 0.001), and tumour doxorubicin concentration (day-1) was significantly higher after HAI of emulsion-2 (20,957 ng/g) than in emulsion-1 (8093 ng/g, p < 0.05) and doxorubicin alone (2221 ng/g, p < 0.01).ConclusionStabilization of doxorubicin in a water-in-oil Lipiodol{sup ®}-based emulsion results in better theranostic properties.

  9. Flow-injection fluorimetric determination of menadione using on-line photo-reduction in micellar media

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Ruiz, Tomas; Martinez-Lozano, Carmen; Tomas, Virginia; Martin, Jesus

    2004-07-01

    A very sensitive fluorimetric method for the determination of menadione using a flow injection system is proposed. The method is based on the on-line reduction of menadione in dodecylsulphate micelles upon irradiation with UV light. The strong fluorescence of the reduced menadione in micellar medium is measured at 410 nm with excitation at 340 nm. The method shows a linear range between 2.42 and 245 ng ml{sup -1} and a limit of detection of 0.18 ng ml{sup -1}. The sample throughput was 90 injections per hour. The applicability of the assay was demonstrated by analysing this vitamin in commercial pharmaceutical preparations.

  10. Flow-injection fluorimetric determination of menadione using on-line photo-reduction in micellar media

    International Nuclear Information System (INIS)

    Perez-Ruiz, Tomas; Martinez-Lozano, Carmen; Tomas, Virginia; Martin, Jesus

    2004-01-01

    A very sensitive fluorimetric method for the determination of menadione using a flow injection system is proposed. The method is based on the on-line reduction of menadione in dodecylsulphate micelles upon irradiation with UV light. The strong fluorescence of the reduced menadione in micellar medium is measured at 410 nm with excitation at 340 nm. The method shows a linear range between 2.42 and 245 ng ml -1 and a limit of detection of 0.18 ng ml -1 . The sample throughput was 90 injections per hour. The applicability of the assay was demonstrated by analysing this vitamin in commercial pharmaceutical preparations

  11. Evaluation of cardiac adrenergic neuronal damage in rats with doxorubicin-induced cardiomyopathy using iodine-131 MIBG autoradiography and PGP 9.5 immunohistochemistry

    International Nuclear Information System (INIS)

    Jeon, T.J.; Lee, J.D.; Ha, J.-W.; Yang, W.I.; Cho, S.H.

    2000-01-01

    Doxorubicin is one of the most useful anticancer agents, but its repeated administration can induce irreversible cardiomyopathy as a major complication. The purpose of this study was to investigate doxorubicin toxicity on cardiac sympathetic neurons using iodine-131-metaiodobenzylguanidine (MIBG) and protein gene product (PGP) 9.5 immunohistochemistry, which is a marker of cardiac innervation. Wistar rats were treated with doxorubicin (2 mg/kg, i.v.) once a week for 4 (n=5), 6 (n=6) or 8 (n=7) weeks consecutively. Left ventricular ejection fraction (LVEF), calculated by M-mode echocardiography, was used as an indicator of cardiac function. Plasma noradrenaline (NA) concentration was measured by high-performance liquid chromatography (HPLC). 131 I-MIBG uptake of the left ventricular wall (24 ROIs) was measured by autoradiography. 131 I-MIBG uptake pattern was compared with histopathological results, the neuronal population on PGP 9.5 immunohistochemistry and the degree of myocyte damage assessed using a visual scoring system on haematoxylin and eosin and Masson's trichrome staining. LVEF was significantly decreased in the 8-week group (P 131 I-MIBG uptake ratio of subepicardium to subendocardium were significantly increased (P<0.05) in the 8-week group as compared with the control group. It may be concluded that radioiodinated MIBG is a reliable marker for the detection of cardiac adrenergic neuronal damage in doxorubicin-induced cardiomyopathy; it detects such damage earlier than do other clinical parameters and in this study showed a good correlation with the reduction in the neuronal population on PGP 9.5 stain. The subendocardial layer appeared to be more vulnerable to doxorubicin than the subepicardium. (orig.)

  12. Mixing in the human carotid artery during carotid drug infusion studied with PET

    International Nuclear Information System (INIS)

    Junck, L.; Koeppe, R.A.; Greenberg, H.S.

    1989-01-01

    The safety and efficacy of drug infusion into the carotid artery require adequate mixing of the infused solution with carotid blood. Using positron emission tomography (PET), we studied the mixing of solutions infused into the human carotid artery in seven patients by analyzing the distribution of [15O]H2O infused into the carotid artery and by vein. At four infusion rates ranging from 0.5 to 10 ml/min, the variability in distribution averaged 16.5-17.8% among the pixels in a large volume of interest, without dependence on the infusion rate. The overall correlation between [15O]H2O influx with arterial infusion and [15O]H2O influx with venous injection was 0.78-0.82 at the four infusion rates, with no trend toward higher correlations at the faster infusion rates. The distribution into the anterior, middle, and posterior cerebral artery territories differed from distribution throughout the entire carotid territory by an average of 6.2-9.6% at the four infusion rates, with no trend toward smaller differences at the faster infusion rates. Infusions performed into a vinyl tube simulating the carotid artery indicated that at 0.5 ml/min, the velocity of fluid exiting the catheter makes no apparent contribution to mixing. We conclude that with infusions at the carotid bifurcation, mixing in the human carotid artery is complete or nearly complete over a wide range of infusion rates. The mixing appears to result from the patterns of blood flow within the artery, and not from jet effects at the catheter tip

  13. Chemotherapeutic Drugs and Mitochondrial Dysfunction: Focus on Doxorubicin, Trastuzumab, and Sunitinib

    Directory of Open Access Journals (Sweden)

    Stefania Gorini

    2018-01-01

    Full Text Available Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible. Vice versa, doxorubicin-induced toxicity not only includes mitochondria damage but can also lead to a more robust and extensive cell injury which is often irreversible and lethal. Drugs interfering with mitochondrial functionality determine the depletion of ATP reservoirs and lead to subsequent reversible contractile dysfunction. Mitochondrial damage includes the impairment of the respiratory chain and the loss of mitochondrial membrane potential with subsequent disruption of cellular energetic. In a context of increased stress, AMPK has a key role in maintaining energy homeostasis, and inhibition of the AMPK pathway is one of the proposed mechanisms possibly mediating mitochondrial toxicity due to chemotherapeutics. Therapies targeting and protecting cell metabolism and energy management might be useful tools in protecting muscular tissues against the toxicity induced by chemotherapeutic drugs.

  14. Suppression of human breast tumors in NOD/SCID mice by CD44 shRNA gene therapy combined with doxorubicin treatment

    Directory of Open Access Journals (Sweden)

    Pham PV

    2012-05-01

    Full Text Available Phuc Van Pham1, Ngoc Bich Vu1, Thuy Thanh Duong1, Tam Thanh Nguyen1, Nhung Hai Truong1, Nhan Lu Chinh Phan1, Tue Gia Vuong1, Viet Quoc Pham1, Hoang Minh Nguyen1, Kha The Nguyen1, Nhung Thi Nguyen1, Khue Gia Nguyen1, Lam Tan Khat1, Dong Van Le2, Kiet Dinh Truong1, Ngoc Kim Phan11Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, HCM City, 2Military Medical University, Ha Noi, VietnamBackground: Breast cancer stem cells with a CD44+CD24- phenotype are the origin of breast tumors. Strong CD44 expression in this population indicates its important role in maintaining the stem cell phenotype. Previous studies show that CD44 down-regulation causes CD44+CD24- breast cancer stem cells to differentiate into non-stem cells that are sensitive to antitumor drugs and lose many characteristics of the original cells. In this study, we determined tumor suppression in non-obese severe combined immunodeficiency mice using CD44 shRNA therapy combined with doxorubicin treatment.Methods: Tumor-bearing non-obese severe combined immunodeficiency mice were established by injection of CD44+CD24- cells. To track CD44+CD24- cells, green fluorescence protein was stably transduced using a lentiviral vector prior to injection into mice. The amount of CD44 shRNA lentiviral vector used for transduction was based on CD44 down-regulation by in vitro CD44 shRNA transduction. Mice were treated with direct injection of CD44 shRNA lentiviral vector into tumors followed by doxorubicin administration after 48 hours. The effect was evaluated by changes in the size and weight of tumors compared with that of the control.Results: The combination of CD44 down-regulation and doxorubicin strongly suppressed tumor growth with significant differences in tumor sizes and weights compared with that of CD44 down-regulation or doxorubicin treatment alone. In the combination of CD44 down-regulation and doxorubicin group, the tumor weight was

  15. Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patient with brain tumor

    International Nuclear Information System (INIS)

    Kosuda, Shigeru; Kusano, Shoichi; Aoki, Shigeki

    1993-01-01

    In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtrained by intraarterial infusion of 18.5 MBq of 99m Tc-d,l,-hexamethylpropyleneamine oxime ( 99m Tc-HMPAO). Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supra- or infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99m Tc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99m Tc-HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99m Tc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99m Tc-HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherpay. (author)

  16. New model system for testing effects of flavonoids on doxorubicin-related formation of hydroxyl radicals

    Czech Academy of Sciences Publication Activity Database

    Souček, P.; Kondrová, E.; Heřmánek, J.; Stopka, Pavel; Boumendjel, A.; Ueng, YF.; Gut, I.

    2011-01-01

    Roč. 22, č. 2 (2011), s. 176-184 ISSN 0959-4973 Institutional research plan: CEZ:AV0Z40320502 Keywords : doxorubicin * electron spin resonance * flavonoids hydroxyl radicals Subject RIV: FD - Oncology ; Hematology Impact factor: 2.407, year: 2011

  17. The Tolerability and Efficacy of Rapid Infliximab Infusions in Patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Qazi, Taha; Shah, Bhavesh; El-Dib, Mohammed; Farraye, Francis A

    2016-02-01

    Few studies have assessed the loss of efficacy or patient and caregiver satisfaction with rapid infliximab infusions. The aim of this study is to assess the tolerability, loss of efficacy and to describe the impact on resource utilization and patient satisfaction in rapid infliximab infusions. Subjects with inflammatory bowel disease receiving rapid infliximab infusions were included in the study. Subjects received maintenance infusions from June 2011 to June 2013. Incidence of adverse reactions and the total number of rapid infliximab infusions were recorded. Efficacy was compared to published studies evaluating the long-term efficacy of infliximab infusions. Patient satisfaction was addressed through a survey following the implementation of the rapid infusion protocol. Seventy-five subjects with IBD were included in the study. Five hundred and twenty-two rapid infliximab infusions were provided to patients. There were no acute or delayed infusion reactions. Ten subjects (13 %) required either a dose escalation or interval adjustment between infliximab infusions. A majority of patients reported increased satisfaction with 1-h infliximab infusions, and 97 % of surveyed patients opted to continue rapid infusions. The rapid infliximab infusion protocol increased infusion unit efficiency by increasing capacity by 15 %. Cost savings in the elimination of nursing time translated to approximately $108,150 savings at our institution. Rapid infliximab infusions do not appear to increase the risk of loss of response compared to historical studies of long-term infliximab efficiency. A rapid infliximab infusion protocol improved efficiency in our infusion unit and increased patient and nursing satisfaction.

  18. Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia.

    Science.gov (United States)

    Comelon, M; Raeder, J; Stubhaug, A; Nielsen, C S; Draegni, T; Lenz, H

    2016-04-01

    The aim of this study was to examine if gradual withdrawal of remifentanil infusion prevented opioid-induced hyperalgesia (OIH) as opposed to abrupt withdrawal. OIH duration was also evaluated. Nineteen volunteers were enrolled in this randomized, double-blinded, placebo-controlled, crossover study. All went through three sessions: abrupt or gradual withdrawal of remifentanil infusion and placebo. Remifentanil was administered at 2.5 ng ml(-1) for 30 min before abrupt withdrawal or gradual withdrawal by 0.6 ng ml(-1) every five min. Pain was assessed at baseline, during infusion, 45-50 min and 105-110 min after end of infusions using the heat pain test (HPT) and the cold pressor test (CPT). The HPT 45 min after infusion indicated OIH development in the abrupt withdrawal session with higher pain scores compared with the gradual withdrawal and placebo sessions (both Pwithdrawal compared with placebo (P=0.93). In the CPT 50 min after end of infusion there was OIH in both remifentanil sessions compared with placebo (gradual P=0.01, abrupt Pwithdrawal of remifentanil infusion in the HPT. After abrupt withdrawal OIH was present in the HPT. In the CPT there was OIH after both gradual and abrupt withdrawal of infusion. The duration of OIH was less than 105 min for both pain modalities. NCT 01702389. EudraCT number 2011-002734-39. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Doxorubicin potentiates TRAIL cytotoxicity and apoptosis and can overcome TRAIL-resistance in rhabdomyosarcoma cells

    NARCIS (Netherlands)

    Komdeur, R; Meijer, C; Van Zweeden, M; De Jong, S; Wesseling, J; Hoekstra, HJ; van der Graaf, WTA

    Doxorubicin (DOX) and ifosfamide (IFO) are the most active single agents in soft tissue sarcomas (STS). Tumour necrosis factor-alpha (TNF-alpha) is used for STS in the setting of isolated limb perfusions. Like TNF-alpha, TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis. In contrast to

  20. Symptomatic Tarlov Cysts: Surgical Treatment by Subcutaneous Infusion Port.

    Science.gov (United States)

    Huang, Ying; Zhu, Tong; Lin, Hongyi; Li, Jing; Zeng, Tao; Lin, Jian

    2018-05-01

    The treatment of Tarlov cysts is challenging and difficult. The objective of our study was to describe the security and efficacy of the subcutaneous infusion port for drainage of symptomatic Tarlov cysts. The authors executed a retrospective review of data from 5 symptomatic Tarlov cysts patients who were treated using a subcutaneous infusion port from June 2014 to July 2017. Numerical Rating Scale scores and the Japanese Orthopedic Association scores of back pain were analyzed. Complications and adverse effects on postoperative days 1, 7, 14, and 28 were also analyzed. The mean follow-up was 12.6 months. Five adults (3 females and 2 males) who had been symptomatic received a subcutaneous infusion port. After treatment, all patients experienced pain relief and pain alleviation lasted from 1 day to 3 years without complications and adverse effects. A subcutaneous infusion port is a useful treatment option for symptomatic Tarlov cysts. When the patients' symptoms returned and the cysts repressurized, we quickly and simply drained the cysts by using the infusion port. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Vacuum infusion manufacturing and experimental characterization of Kevlar/epoxy composites

    International Nuclear Information System (INIS)

    Ricciardi, M. R.; Giordano, M.; Antonucci, V.; Langella, A.; Nele, L.

    2014-01-01

    Epoxy/Kevlar composites have been manufactured by conventional Vacuum Infusion process and the Pulse Infusion technique. Pulse Infusion allows to control the pressure of the vacuum bag on the dry fiber reinforcement by using a proper designed pressure distributor that induces a pulsed transverse action and promotes the through thickness resin flow. The realized composite panel have been mechanically characterized by performing tensile and short beam shear tests according with the ASTM D3039 and ASTM D2344/D 2344M standard respectively in order to investigate the effect of Pulse Infusion on the tensile strength and ILSS

  2. Vacuum infusion manufacturing and experimental characterization of Kevlar/epoxy composites

    Science.gov (United States)

    Ricciardi, M. R.; Giordano, M.; Langella, A.; Nele, L.; Antonucci, V.

    2014-05-01

    Epoxy/Kevlar composites have been manufactured by conventional Vacuum Infusion process and the Pulse Infusion technique. Pulse Infusion allows to control the pressure of the vacuum bag on the dry fiber reinforcement by using a proper designed pressure distributor that induces a pulsed transverse action and promotes the through thickness resin flow. The realized composite panel have been mechanically characterized by performing tensile and short beam shear tests according with the ASTM D3039 and ASTM D2344/D 2344M standard respectively in order to investigate the effect of Pulse Infusion on the tensile strength and ILSS.

  3. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Four new degradation products of doxorubicin: An application of forced degradation study and hyphenated chromatographic techniques

    Directory of Open Access Journals (Sweden)

    Dheeraj Kaushik

    2015-10-01

    Full Text Available Forced degradation study on doxorubicin (DOX was carried out under hydrolytic condition in acidic, alkaline and neutral media at varied temperatures, as well as under peroxide, thermal and photolytic conditions in accordance with International Conference on Harmonization (ICH guidelines Q1(R2. It was found extremely unstable to alkaline hydrolysis even at room temperature, unstable to acid hydrolysis at 80 °C, and to oxidation at room temperature. It degraded to four products (O-I–O-IV in oxidative condition, and to single product (A-I in acid hydrolytic condition. These products were resolved on a C8 (150 mm×4.6 mm, 5 µm column with isocratic elution using mobile phase consisting of HCOONH4 (10 mM, pH 2.5, acetonitrile and methanol (65:15:20, v/v/v. Liquid chromatography–photodiode array (LC–PDA technique was used to ascertain the purity of the products noted in LC–UV chromatogram. For their characterization, a six stage mass fragmentation (MS6 pattern of DOX was outlined through mass spectral studies in positive mode of electrospray ionization (+ESI as well as through accurate mass spectral data of DOX and the products generated through liquid chromatography–time of flight mass spectrometry (LC–MS–TOF on degraded drug solutions. Based on it, O-I–O-IV were characterized as 3-hydroxy-9-desacetyldoxorubicin-9-hydroperoxide, 1-hydroxy-9-desacetyldoxorubicin-9-hydroperoxide, 9-desacetyldoxorubicin-9-hydroperoxide and 9-desacetyldoxorubicin, respectively, whereas A-I was characterized as deglucosaminyl doxorubicin. While A-I was found to be a pharmacopoeial impurity, all oxidative products were found to be new degradation impurities. The mechanisms and pathways of degradation of doxorubicin were outlined and discussed. Keywords: Doxorubicin, TOF, Forced degradation, Liquid chromatography, Degradation product, Mass fragmentation pattern

  5. Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

    Science.gov (United States)

    Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

    2017-10-01

    A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway

    International Nuclear Information System (INIS)

    Shimada, Kana; Saeki, Makio; Egusa, Hiroshi; Fukuyasu, Sho; Yura, Yoshiaki; Iwai, Kazuhiro; Kamisaki, Yoshinori

    2011-01-01

    Research highlights: → RNA polymerase II-associated protein 3 (RPAP3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO. → RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. → RPAP3 is a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents. -- Abstract: Activation of anti-apoptotic gene transcription by NF-κB (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-κB essential modulator) interacts with a number of proteins and modulates the activity of NF-κB pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. These results indicate that RPAP3 may be a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents.

  7. p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance

    International Nuclear Information System (INIS)

    Yang, Ji Yeon; Ha, Seon-Ah; Yang, Yun-Sik; Kim, Jin Woo

    2010-01-01

    Cancer cells recurrently develop into acquired resistance to the administered drugs. The iatrogenic mechanisms of induced chemotherapy-resistance remain elusive and the degree of drug resistance did not exclusively correlate with reductions of drug accumulation, suggesting that drug resistance may involve additional mechanisms. Our aim is to define the potential targets, that makes drug-sensitive MCF-7 breast cancer cells turn to drug-resistant, for the anti-cancer drug development against drug resistant breast cancer cells. Doxorubicin resistant human breast MCF-7 clones were generated. The doxorubicin-induced cell fusion events were examined. Heterokaryons were identified and sorted by FACS. In the development of doxorubicin resistance, cell-fusion associated genes, from the previous results of microarray, were verified using dot blot array and quantitative RT-PCR. The doxorubicin-induced expression patterns of pro-survival and pro-apoptotic genes were validated. YB-1 and ABCB5 were up regulated in the doxorubicin treated MCF-7 cells that resulted in certain degree of genomic instability that accompanied by the drug resistance phenotype. Cell fusion increased diversity within the cell population and doxorubicin resistant MCF-7 cells emerged probably through clonal selection. Most of the drug resistant hybrid cells were anchorage independent. But some of the anchorage dependent MCF-7 cells exhibited several unique morphological appearances suggesting minor population of the fused cells maybe de-differentiated and have progenitor cell like characteristics. Our work provides valuable insight into the drug induced cell fusion event and outcome, and suggests YB-1, GST, ABCB5 and ERK3 could be potential targets for the anti-cancer drug development against drug resistant breast cancer cells. Especially, the ERK-3 serine/threonine kinase is specifically up-regulated in the resistant cells and known to be susceptible to synthetic antagonists

  8. Online naphazoline quality control by micellar-enhanced spectrofluorimetry.

    Science.gov (United States)

    Peralta, Cecilia Mariana; Silva, Raúl Alejandro; Fernández, Liliana Patricia; Masi, Adriana Noemí

    2011-01-01

    The aim of this study was to develop a method for online spectrofluorimetric quality control of naphazoline (NPZ) in pharmaceuticals and raw drugs. A combination of a flow-injection analysis (FIA) system with micellar-enhanced fluorescence detection is presented as a powerful alternative for the rapid and sensitive analysis of naphazoline. Since NPZ shows low native fluorescence, the use of an anionic surfactant, such as sodium dodecyl sulphate (SDS), provides a considerable enhancement of fluorescence intensity and the nature of the technique allows a possible and easy adaptation to a FIA system. Using λ(exc) = 280 nm and λ(em) = 326 nm, a good linear relationship (LOL) was obtained in the range 0.003-10 µg mL(-1) with a detection limit (LOD) of 3 × 10(-4) µg mL(-1) (s/n = 3). Parameters related to the nature of the analytical signal and to the FIA manifold were optimized. Satisfactory recoveries were obtained in the analysis of commercial pharmaceutical formulations. The proposed method is simple, accurate and allows for high-speed sampling and considerably shorter analysis times. In addition, it requires inexpensive equipment and reagents and has easy operational conditions and no side effects, thus avoiding environmental pollution through toxic waste. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Separation Of N-Nitrosamines By Micellar Electrokinetic Chromatography

    International Nuclear Information System (INIS)

    Nur Amira Md Ali; Mohd Marsin Sanagi; Wan Aini Wan Ibrahim

    2014-01-01

    A simple and rapid micellar electrokinetic chromatography (MEKC) method was developed for separation of three selected N-Nitrosamines namely N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA) and N-nitrosodiphenylamine (NDPhA). The effects of composition of the buffer and its pH, concentration of surfactants on the separation and migration times of nitrosamines were investigated. The instrumental variables affecting sensitivity and resolution such as power supply and injection mode were carefully optimized. The best separation was achieved using 40 mM sodium dodecyl sulfate (SDS) as a surfactant in 10 mM phosphate buffer (pH 8.0) at a temperature of 25 degree Celsius, applied voltage of 29 kV, wavelength of 230 nm and electrokinetic injection of 9 s at 5 kV within 10 min analysis time. Excellent linearity was obtained in the concentration range of 2 to 100 μg/ mL with coefficients of determination, r 2 ≥0.979. This method showed good reproducibility with relative standard deviation (RSDs) value ranging from 2.46 % to 6.61 %. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 0.16 to 0.43 μg/ mL and 0.54 to 1.44 μg/mL respectively. (author)

  10. Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Jacobsen, Soren

    2013-01-01

    To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre......-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events...... (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient...

  11. Studies on the effect of doxorubicin on MDA, NO 2 , NO 3 , Se-GSH ...

    African Journals Online (AJOL)

    Doxorubicin, a highly effective anticancer drug, produces cardiotoxicity, which limits its therapeutic potential. The mechanism of this cardiotoxicity has remained elusive. The use of this drug, however, continues to be limited by its dose-related and time interval toxicity. Reactive oxygen species are hypothesized to be a major ...

  12. SALT-INDUCED TRANSITION FROM A MICELLAR TO A LAMELLAR LIQUID-CRYSTALLINE PHASE IN DILUTE MIXTURES OF ANIONIC AND NONIONIC SURFACTANTS IN AQUEOUS-SOLUTION

    NARCIS (Netherlands)

    SEIN, A; ENGBERTS, JBFN; VANDERLINDEN, E; VANDEPAS, JC

    In dilute mixtures of anionic surfactant, sodium dodecylbenzenesulfonate (NaDoBS), and nonionic poly(ethylene oxide) alkyl monoether (C13-15E(7)) a transition from a micellar to a lamellar phase is found at high salting-out electrolyte (NaCit) concentrations. With an increase of the salt

  13. Infusion of iloprost without a peristaltic pump: Safety and tolerability

    Directory of Open Access Journals (Sweden)

    Paola Faggioli

    2013-04-01

    Full Text Available Introduction: Iloprost is a potent prostacyclin (PGI2 analogue that is effective in the treatment of peripheral arterial disease, vasculitis, pulmonary hypertension, and secondary Raynaud’s phenomenon. Intravenous infusions are generally administered with the aid of a peristaltic pump to reduce the risk of adverse reactions caused by unintentional increases in the infusion rate. This increases the cost of care in terms of equipment and personnel and may limit the use of this drug. Materials and methods: We retrospectively analyzed 18,432 iloprost infusions administered between 1999 and 2009 to 272 patients with systemic sclerosis (n = 253 and 19 with peripheral arterial disease (n = 19. All infusions were administered in the day hospital over 6 h with a normal IV set-up with a roller flow regulator. Flow rates were set to deliver iloprost at 1-2 ng/kg/min. Rates were verified by direct drop counts during the first 15-20 minutes of the infusion and at each subsequent check. Results: There were no adverse events that were fatal, life-threatening, or associated with prolongation of hospitalization and very few events requiring intensive care or continuous monitoring. The latter included 4 cases of tachycardia/arrhythmia (extrasystoles in most cases, 3 cases of hypotension (systolic pressure < 80 mmHg, and 2 cases of hypertension (BP > 170/100 mmHg. All other adverse reactions were mild, reversible, and similar to those seen with iloprost infusion with peristaltic pump. Only one patient had to be switched to another prostanoid (due to intolerance. Discussion: Iloprost infusion administered with a normal IV flow regulator appears to be as safe, well tolerated, and effective as traditional infusion with a peristaltic pump.

  14. Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion

    DEFF Research Database (Denmark)

    Kousholt, Birgitte S.; Larsen, Jens Kjærgaard Rolighed; Bisgaard, Line Stattau

    2012-01-01

    Aim: The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia–reperfusion damage. Materials and methods: The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect...... in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (~15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared...... with controls (P=0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P=0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P=0.0015 and 0.0019), and were associated with improved RNA integrity...

  15. Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion

    DEFF Research Database (Denmark)

    Kousholt, Birgitte S.; Larsen, Jens Kjærgaard Rolighed; Bisgaard, Line Stattau

    2012-01-01

    Aim: The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia–reperfusion damage. Materials and methods: The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect...... in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (∼15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared...... with controls (P=0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P=0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P=0.0015 and 0.0019), and were associated with improved RNA integrity...

  16. Aluminum bioavailability from tea infusion.

    Science.gov (United States)

    Yokel, Robert A; Florence, Rebecca L

    2008-12-01

    The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer (26)Al. (26)Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous (27)Al infusion. Oral Al bioavailability (F) was calculated from the area under the (26)Al, compared to (27)Al, serum concentration x time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F=0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F=0.1-0.3%), but greater than acidic SALP in a biscuit (F=0.1%). Time to maximum serum (26)Al concentration was 1.25, 1.5, 8 and 4.8h, respectively. These results of oral Al bioavailability x daily consumption by the human suggest tea can provide a significant amount of the Al that reaches systemic circulation. This can allow distribution to its target organs of toxicity, the central nervous, skeletal and hematopoietic systems. Further testing of the hypothesis that Al contributes to Alzheimer's disease may be more warranted with studies focusing on total average daily food intake, including tea and other foods containing appreciable Al, than drinking water.

  17. Loading and release of doxorubicin with magnetic nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xia; Wang, Xiang; Lee, Sang Bok [Dept. of Chemistry and Biochemistry, University of Maryland, College Park (United States); English, Douglas [Dept. of Chemistry, Wichita State University, Wichita (United States)

    2015-03-15

    In this work, we study magnetic nanotubes (MNTs) as drug carriers to control the loading and release of doxorubicin (Dox). The inner surfaces of MNTs where Dox molecules are stored are modified with C18-silane and pyridine–silane. By tuning the interaction between the drug molecules and inner surfaces of MNTs via pH, Dox can be effectively encapsulated at pH 7.2 and released at pH 4.5. The successful loading of Dox is confirmed with confocal microscopy studies. The release profiles of Dox from modified MNTs are detected by spectrofluorophotometry, with bare MNTs as control. With proper modifications, MNTs can be used for pH-dependent, controlled release of drug molecules.

  18. Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion

    NARCIS (Netherlands)

    Heetla, H. W.; Staal, M. J.; van Laar, T.

    Study design: Pilot study. Objective: To study the effect of pulsatile bolus infusion of intrathecal baclofen (ITB) on daily ITB dose, in patients showing dose increases, probably due to tolerance. Setting: Department of neurology and neurosurgery, University Medical Center Groningen, the

  19. Binding of chloroquine to ionic micelles: Effect of pH and micellar surface charge

    Energy Technology Data Exchange (ETDEWEB)

    Souza Santos, Marcela de, E-mail: marcelafarmausp77@gmail.com [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, Ribeirão Preto, São Paulo 14040-903 (Brazil); Perpétua Freire de Morais Del Lama, Maria, E-mail: mpemdel@fcfrp.usp.br [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, Ribeirão Preto, São Paulo 14040-903 (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Departamento de Química Analítica, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, s/n, Campinas, São Paulo 13083-970 (Brazil); Siuiti Ito, Amando, E-mail: amandosi@ffclrp.usp.br [Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo 14040-901 (Brazil); and others

    2014-03-15

    The pharmacological action of chloroquine relies on its ability to cross biological membranes in order to accumulate inside lysosomes. The present work aimed at understanding the basis for the interaction between different chloroquine species and ionic micelles of opposite charges, the latter used as a simple membrane model. The sensitivity of absorbance and fluorescence of chloroquine to changes in its local environment was used to probe its interaction with cetyltrimethylammonium micelles presenting bromide (CTAB) and sulfate (CTAS) as counterions, in addition to dodecyl sulfate micelles bearing sodium (SDS) and tetramethylammonium (TMADS) counterions. Counterion exchange was shown to have little effect on drug–micelle interaction. Chloroquine first dissociation constant (pKa{sub 1}) shifted to opposite directions when anionic and cationic micelles were compared. Chloroquine binding constants (K{sub b}) revealed that electrostatic forces mediate charged drug–micelle association, whereas hydrophobic interactions allowed neutral chloroquine to associate with anionic and cationic micelles. Fluorescence quenching studies indicated that monoprotonated chloroquine is inserted deeper into the micelle surface of anionic micelles than its neutral form, the latter being less exposed to the aqueous phase when associated with cationic over anionic assemblies. The findings provide further evidence that chloroquine–micelle interaction is driven by a tight interplay between the drug form and the micellar surface charge, which can have a major effect on the drug biological activity. -- Highlights: • Chloroquine (CQ) pKa{sub 1} increased for SDS micelles and decreased for CTAB micelles. • CQ is solubilized to the surface of both CTAB and SDS micelles. • Monoprotonated CQ is buried deeper into SDS micelles than neutral CQ. • Neutral CQ is less exposed to aqueous phase in CTAB over SDS micelles. • Local pH and micellar surface charge mediate interaction of CQ with

  20. Structural changes induced by high-pressure processing in micellar casein and milk protein concentrates.

    Science.gov (United States)

    Cadesky, Lee; Walkling-Ribeiro, Markus; Kriner, Kyle T; Karwe, Mukund V; Moraru, Carmen I

    2017-09-01

    Reconstituted micellar casein concentrates and milk protein concentrates of 2.5 and 10% (wt/vol) protein concentration were subjected to high-pressure processing at pressures from 150 to 450 MPa, for 15 min, at ambient temperature. The structural changes induced in milk proteins by high-pressure processing were investigated using a range of physical, physicochemical, and chemical methods, including dynamic light scattering, rheology, mid-infrared spectroscopy, scanning electron microscopy, proteomics, and soluble mineral analyses. The experimental data clearly indicate pressure-induced changes of casein micelles, as well as denaturation of serum proteins. Calcium-binding α S1 - and α S2 -casein levels increased in the soluble phase after all pressure treatments. Pressurization up to 350 MPa also increased levels of soluble calcium and phosphorus, in all samples and concentrations, whereas treatment at 450 MPa reduced the levels of soluble Ca and P. Experimental data suggest dissociation of calcium phosphate and subsequent casein micelle destabilization as a result of pressure treatment. Treatment of 10% micellar casein concentrate and 10% milk protein concentrate samples at 450 MPa resulted in weak, physical gels, which featured aggregates of uniformly distributed, casein substructures of 15 to 20 nm in diameter. Serum proteins were significantly denatured by pressures above 250 MPa. These results provide information on pressure-induced changes in high-concentration protein systems, and may inform the development on new milk protein-based foods with novel textures and potentially high nutritional quality, of particular interest being the soft gel structures formed at high pressure levels. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).