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  1. Article ; Online: Flux-P

    Birgitta E. Ebert / Anna-Lena Lamprecht / Bernhard Steffen / Lars M. Blank

    Metabolites, Vol 2, Iss 4, Pp 872-

    Automating Metabolic Flux Analysis

    2012  Volume 890

    Abstract: ... for data interpretation to a rather small number of experiments. In this paper, we present Flux-P ...

    Abstract Quantitative knowledge of intracellular fluxes in metabolic networks is invaluable for inferring metabolic system behavior and the design principles of biological systems. However, intracellular reaction rates can not often be calculated directly but have to be estimated; for instance, via 13C-based metabolic flux analysis, a model-based interpretation of stable carbon isotope patterns in intermediates of metabolism. Existing software such as FiatFlux, OpenFLUX or 13CFLUX supports experts in this complex analysis, but requires several steps that have to be carried out manually, hence restricting the use of this software for data interpretation to a rather small number of experiments. In this paper, we present Flux-P as an approach to automate and standardize 13C-based metabolic flux analysis, using the Bio-jETI workflow framework. Exemplarily based on the FiatFlux software, it demonstrates how services can be created that carry out the different analysis steps autonomously and how these can subsequently be assembled into software workflows that perform automated, high-throughput intracellular flux analysis of high quality and reproducibility. Besides significant acceleration and standardization of the data analysis, the agile workflow-based realization supports flexible changes of the analysis workflows on the user level, making it easy to perform custom analyses.
    Keywords 13C metabolic flux analysis ; MFA ; high-throughput analysis ; scientific workflows ; workflow management ; Bio-jETI ; Biochemistry ; QD415-436 ; Organic chemistry ; QD241-441 ; Chemistry ; QD1-999 ; Science ; Q ; DOAJ:Biochemistry ; DOAJ:Life Sciences ; DOAJ:Biology and Life Sciences
    Subject code 004
    Language English
    Publishing date 2012-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: P-glycoprotein inhibition of drug resistant cell lines by nanoparticles.

    Singh, Manu Smriti / Lamprecht, Alf

    Drug development and industrial pharmacy

    2016  Volume 42, Issue 2, Page(s) 325–331

    Abstract: ... cell interaction and accumulation of P-glycoprotein (P-gp) substrates-rhodamine-123 and calcein AM, in highly drug ... highest P-gp modulatory activity in both free solution form (up to 7-fold lower IC50) and as a formulation ...

    Abstract Several pharmaceutical excipients are known for their ability to interact with cell membrane lipids and reverse the phenomenon of multidrug resistance (MDR) in cancer. Interestingly, many excipients act as stabilizers and are key ingredients in a variety of nano-formulations. In this study, representatives of ionic and non-ionic excipients were used as surface active agents in nanoparticle (NP) formulations to utilize their MDR reversing potential. In-vitro assays were performed to elucidate particle-cell interaction and accumulation of P-glycoprotein (P-gp) substrates-rhodamine-123 and calcein AM, in highly drug resistant glioma cell lines. Chemosensitization achieved using NPs and their equivalent dose of free excipients was assessed with the co-administered anti-cancer drug doxorubicin. Among the excipients used, non-ionic surfactant, Cremophor® EL, and cationic surfactant, cetyltrimethylammonuium bromide (CTAB), demonstrated highest P-gp modulatory activity in both free solution form (up to 7-fold lower IC50) and as a formulation (up to 4.7-fold lower IC50) as compared to doxorubicin treatment alone. Solutol® HS15 and Tween® 80 exhibited considerable chemosensitization as free solution but not when incorporated into a formulation. Sodium dodecyl sulphate (SDS)-based nanocarriers resulted in slightly improved cytotoxicity. Overall, the results highlight and envisage the usage of excipient in nano-formulations in a bid to improve chemosensitization of drug resistant cancer cells towards anti-cancer drugs.
    MeSH term(s) ATP-Binding Cassette, Sub-Family B, Member 1/antagonists & inhibitors ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Animals ; Antibiotics, Antineoplastic/administration & dosage ; Antibiotics, Antineoplastic/pharmacology ; Cell Line, Tumor ; Chemistry, Pharmaceutical/methods ; Doxorubicin/administration & dosage ; Doxorubicin/pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Excipients/chemistry ; Excipients/pharmacology ; Fluoresceins/metabolism ; Glioma/drug therapy ; Glioma/pathology ; Inhibitory Concentration 50 ; Nanoparticles ; Rats ; Rhodamine 123/metabolism ; Surface-Active Agents/chemistry ; Surface-Active Agents/pharmacology
    Chemical Substances ATP-Binding Cassette, Sub-Family B, Member 1 ; Antibiotics, Antineoplastic ; Excipients ; Fluoresceins ; Surface-Active Agents ; calcein AM (148504-34-1) ; Rhodamine 123 (1N3CZ14C5O) ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2016
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 751874-2
    ISSN 1520-5762 ; 0363-9045
    ISSN (online) 1520-5762
    ISSN 0363-9045
    DOI 10.3109/03639045.2015.1054396
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Evaluation of dual P-gp-BCRP inhibitors as nanoparticle formulation.

    Singh, Manu Smriti / Juvale, Kapil / Wiese, Michael / Lamprecht, Alf

    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

    2015  Volume 77, Page(s) 1–8

    Abstract: ... to develop inhibitors against the most characterized and ubiquitous MDR transporters: P-glycoprotein (P ... compounds 1 and 2), demonstrate potential MDR reversal activity against BCRP and to a lesser extent, P ... activity in relevant BCRP and P-gp over-expressing cell line models. Particles in the size range 300-365nm ...

    Abstract Overcoming multidrug resistance (MDR) in cancer is a major challenge and efforts are on-going to develop inhibitors against the most characterized and ubiquitous MDR transporters: P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1) and breast cancer resistance protein (BCRP). Recently reported, two 4-anilinoquinazolines (compounds 1 and 2), demonstrate potential MDR reversal activity against BCRP and to a lesser extent, P-gp. In this work, we formulated the compounds as polymeric nanoparticles (NPs) and assessed their MDR inhibitory activity in relevant BCRP and P-gp over-expressing cell line models. Particles in the size range 300-365nm with a loading efficiency of 69% (compound 1 NP) and 77% (compound 2 NP) respectively were obtained. BCRP inhibition was observed in Hoechst 33342 and pheophorbide A assays while P-gp inhibition was evaluated in calcein AM and rhodamine-123 assays. In cytotoxicity studies, while BCRP expressing cells showed complete reversal of drug resistance in nearly all treatment groups (both compounds and their respective NP); a higher reversal in NP treated group was obtained as compared with inhibitory compound treated group in P-gp expressing cells. These results demonstrate promising inhibitory activity of both formulations, especially against P-gp expressing cells; which is possibly due to a prolonged presence of encapsulated compounds in NPs and consequently a prolonged sensitization of transmembrane drug transporter. These formulations can therefore be considered as dual-transporter inhibitors and it is imperative to investigate both inhibitors in animal models of MDR owing to the presence of multiple efflux transporters in several cancer models.
    MeSH term(s) ATP Binding Cassette Transporter, Sub-Family B/antagonists & inhibitors ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters/antagonists & inhibitors ; Animals ; Benzimidazoles/metabolism ; Camptothecin/analogs & derivatives ; Camptothecin/pharmacology ; Chemistry, Pharmaceutical ; Chlorophyll/analogs & derivatives ; Chlorophyll/metabolism ; Dogs ; Doxorubicin/pharmacology ; Madin Darby Canine Kidney Cells ; Microscopy, Confocal ; Nanoparticles ; Neoplasm Proteins/antagonists & inhibitors ; Rhodamine 123/metabolism
    Chemical Substances ABCG2 protein, human ; ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; Benzimidazoles ; Neoplasm Proteins ; Chlorophyll (1406-65-1) ; Rhodamine 123 (1N3CZ14C5O) ; irinotecan (7673326042) ; Doxorubicin (80168379AG) ; pheophorbide a (IA2WNI2HO2) ; bisbenzimide ethoxide trihydrochloride (P976261J69) ; Camptothecin (XT3Z54Z28A)
    Language English
    Publishing date 2015-09-18
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1154366-8
    ISSN 1879-0720 ; 0928-0987
    ISSN (online) 1879-0720
    ISSN 0928-0987
    DOI 10.1016/j.ejps.2015.04.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Flux-p: automating metabolic flux analysis.

    Ebert, Birgitta E / Lamprecht, Anna-Lena / Steffen, Bernhard / Blank, Lars M

    Metabolites

    2012  Volume 2, Issue 4, Page(s) 872–890

    Abstract: ... for data interpretation to a rather small number of experiments. In this paper, we present Flux-P ...

    Abstract Quantitative knowledge of intracellular fluxes in metabolic networks is invaluable for inferring metabolic system behavior and the design principles of biological systems. However, intracellular reaction rates can not often be calculated directly but have to be estimated; for instance, via 13C-based metabolic flux analysis, a model-based interpretation of stable carbon isotope patterns in intermediates of metabolism. Existing software such as FiatFlux, OpenFLUX or 13CFLUX supports experts in this complex analysis, but requires several steps that have to be carried out manually, hence restricting the use of this software for data interpretation to a rather small number of experiments. In this paper, we present Flux-P as an approach to automate and standardize 13C-based metabolic flux analysis, using the Bio-jETI workflow framework. Exemplarily based on the FiatFlux software, it demonstrates how services can be created that carry out the different analysis steps autonomously and how these can subsequently be assembled into software workflows that perform automated, high-throughput intracellular flux analysis of high quality and reproducibility. Besides significant acceleration and standardization of the data analysis, the agile workflow-based realization supports flexible changes of the analysis workflows on the user level, making it easy to perform custom analyses.
    Language English
    Publishing date 2012-11-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo2040872
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: GeneFisher-P

    Lamprecht Anna-Lena / Margaria Tiziana / Steffen Bernhard / Sczyrba Alexander / Hartmeier Sven / Giegerich Robert

    BMC Bioinformatics, Vol 9, Iss Suppl 4, p S

    variations of GeneFisher as processes in Bio-jETI

    2008  Volume 13

    Abstract: ... workflow techniques. We apply a service-oriented approach to model and implement GeneFisher-P , a process ... Conclusions The resulting service- and process-oriented GeneFisher-P demonstrates how basic services ...

    Abstract Abstract Background PCR primer design is an everyday, but not trivial task requiring state-of-the-art software. We describe the popular tool GeneFisher and explain its recent restructuring using workflow techniques. We apply a service-oriented approach to model and implement GeneFisher-P , a process-based version of the GeneFisher web application, as a part of the Bio-jETI platform for service modeling and execution. We show how to introduce a flexible process layer to meet the growing demand for improved user-friendliness and flexibility. Results Within Bio-jETI, we model the process using the jABC framework, a mature model-driven, service-oriented process definition platform. We encapsulate remote legacy tools and integrate web services using jETI, an extension of the jABC for seamless integration of remote resources as basic services, ready to be used in the process. Some of the basic services used by GeneFisher are in fact already provided as individual web services at BiBiServ and can be directly accessed. Others are legacy programs, and are made available to Bio-jETI via the jETI technology. The full power of service-based process orientation is required when more bioinformatics tools, available as web services or via jETI, lead to easy extensions or variations of the basic process. This concerns for instance variations of data retrieval or alignment tools as provided by the European Bioinformatics Institute (EBI). Conclusions The resulting service- and process-oriented GeneFisher-P demonstrates how basic services from heterogeneous sources can be easily orchestrated in the Bio-jETI platform and lead to a flexible family of specialized processes tailored to specific tasks.
    Keywords Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
    Subject code 004
    Language English
    Publishing date 2008-04-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Coadministration of P-glycoprotein modulators on loperamide pharmacokinetics and brain distribution.

    Montesinos, Rita Nieto / Moulari, Brice / Gromand, Jessica / Beduneau, Arnaud / Lamprecht, Alf / Pellequer, Yann

    Drug metabolism and disposition: the biological fate of chemicals

    2014  Volume 42, Issue 4, Page(s) 700–706

    Abstract: The efflux transporter P-glycoprotein, expressed at high levels at the blood-brain barrier, exerts ... central nervous system pharmacotherapies. This study explored the impact of the intravenous coadministration of two P ... a P-glycoprotein substrate probe, in rats. After 1 hour postdosing, tariquidar and elacridar ...

    Abstract The efflux transporter P-glycoprotein, expressed at high levels at the blood-brain barrier, exerts a profound effect on the disposition of various therapeutic compounds in the brain. A rapid and efficient modulation of this efflux transporter could enhance the distribution of its substrates and thereby improve central nervous system pharmacotherapies. This study explored the impact of the intravenous coadministration of two P-glycoprotein modulators, tariquidar and elacridar, on the pharmacokinetics and brain distribution of loperamide, a P-glycoprotein substrate probe, in rats. After 1 hour postdosing, tariquidar and elacridar, both at a dose of 1.0 mg/kg, increased loperamide levels in the brain by 2.3- and 3.5-fold, respectively. However, the concurrent administration of both P-glycoprotein modulators, each at a dose of 0.5 mg/kg, increased loperamide levels in the brain by 5.8-fold and resulted in the most pronounced opioid-induced clinical signs. This phenomenon may be the result of a combined noncompetitive modulation by tariquidar and elacridar. Besides, the simultaneous administration of elacridar and tariquidar did not significantly modify the pharmacokinetic parameters of loperamide. This observation potentially allows the concurrent use of low but therapeutic doses of P-gp modulators to achieve full inhibitory effects.
    MeSH term(s) ATP-Binding Cassette, Sub-Family B, Member 1/antagonists & inhibitors ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Acridines/administration & dosage ; Acridines/pharmacology ; Analgesics/administration & dosage ; Analgesics/blood ; Analgesics/pharmacokinetics ; Analgesics/pharmacology ; Animals ; Brain/drug effects ; Brain/metabolism ; Chromatography, High Pressure Liquid ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Loperamide/administration & dosage ; Loperamide/blood ; Loperamide/pharmacokinetics ; Loperamide/pharmacology ; Male ; Mass Spectrometry ; Quinolines/administration & dosage ; Quinolines/blood ; Quinolines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu/agonists ; Tetrahydroisoquinolines/administration & dosage ; Tetrahydroisoquinolines/blood ; Tetrahydroisoquinolines/pharmacology ; Tissue Distribution
    Chemical Substances ATP-Binding Cassette, Sub-Family B, Member 1 ; Acridines ; Analgesics ; Quinolines ; Receptors, Opioid, mu ; Tetrahydroisoquinolines ; Loperamide (6X9OC3H4II) ; tariquidar (J58862DTVD) ; Elacridar (N488540F94)
    Language English
    Publishing date 2014-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.113.055566
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cargoing P-gp inhibitors via nanoparticle sensitizes tumor cells against doxorubicin.

    Singh, Manu Smriti / Lamprecht, Alf

    International journal of pharmaceutics

    2015  Volume 478, Issue 2, Page(s) 745–752

    Abstract: ... generation P-gp inhibitors- verapamil and elacridar respectively in non-ionic, anionic and ... cationic surfactant-based NPs. The ability of NPs to reverse P-glycoprotein (P-gp)-mediated MDR efflux was evaluated ...

    Abstract Inhibitors against multidrug resistance (MDR) efflux transporters have failed in most clinical settings due to unfavorable pharmacokinetic interactions with co-administered anti-cancer drug and their inherent toxicities. Nanoparticles (NPs) have shown potential to overcome drug efflux by delivering and localizing therapeutic molecules within tumor mass. In this work, we investigated effect of nanocarrier surface charge and formulation parameters for a hydrophilic and lipophilic MDR inhibitor on their ability to reverse drug resistance. Active inhibition of efflux pumps was achieved by encapsulating first and third generation P-gp inhibitors- verapamil and elacridar respectively in non-ionic, anionic and cationic surfactant-based NPs. The ability of NPs to reverse P-glycoprotein (P-gp)-mediated MDR efflux was evaluated in sensitive (A2780) and resistant (A2780Adr) ovarian cancer cell lines by various in vitro accumulation and cytotoxicity assays. Uptake mechanism for NP appears to be caveolae-dependent with 20%-higher internalization in A2780Adr than A2780 cell lines which can be co-related to the biophysical membrane composition. Cationic- CTAB NPs showed highest reversal efficacy followed by PVA and SDS-NP (P+S NP) and PVA-NPs. As compared to doxorubicin treated drug resistant cells lines, blank-, verapamil- and elacridar-CTAB-NPs showed 2.6-, 20- and 193-fold lower IC50 values. This work highlights the importance of inhibitor-loaded charged particles to overcome cancer drug resistance.
    MeSH term(s) ATP-Binding Cassette, Sub-Family B, Member 1/antagonists & inhibitors ; Acridines/administration & dosage ; Acridines/chemistry ; Antibiotics, Antineoplastic/pharmacology ; Cell Line, Tumor ; Cell Survival ; Doxorubicin/pharmacology ; Drug Carriers/administration & dosage ; Drug Carriers/chemistry ; Drug Resistance, Neoplasm ; Humans ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Neoplasms/metabolism ; Polyvinyl Alcohol/chemistry ; Sodium Dodecyl Sulfate/chemistry ; Surface-Active Agents/chemistry ; Tetrahydroisoquinolines/administration & dosage ; Tetrahydroisoquinolines/chemistry ; Verapamil/administration & dosage ; Verapamil/chemistry
    Chemical Substances ATP-Binding Cassette, Sub-Family B, Member 1 ; Acridines ; Antibiotics, Antineoplastic ; Drug Carriers ; Surface-Active Agents ; Tetrahydroisoquinolines ; Sodium Dodecyl Sulfate (368GB5141J) ; Doxorubicin (80168379AG) ; Polyvinyl Alcohol (9002-89-5) ; Verapamil (CJ0O37KU29) ; Elacridar (N488540F94)
    Language English
    Publishing date 2015-01-30
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2014.11.064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Triterpenoid Saponins from the Caryophyllaceae Family Modulate the Efflux Activity of the P-Glycoprotein in an In Vitro Model of Intestinal Barrier.

    Dubray, Océane / Moulari, Brice / Chrétien, Claire / Pellequer, Yann / Lamprecht, Alf / Mitaine-Offer, Anne-Claire / Lacaille-Dubois, Marie-Aleth / Béduneau, Arnaud

    Planta medica

    2016  Volume 82, Issue 18, Page(s) 1553–1557

    Abstract: ... The ... ...

    Abstract The oral
    MeSH term(s) ATP-Binding Cassette, Sub-Family B, Member 1/antagonists & inhibitors ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Caco-2 Cells ; Caryophyllaceae/chemistry ; Humans ; Intestines/metabolism ; Permeability/drug effects ; Saponins/isolation & purification ; Saponins/pharmacology ; Triterpenes/isolation & purification ; Triterpenes/pharmacology
    Chemical Substances ATP-Binding Cassette, Sub-Family B, Member 1 ; Saponins ; Triterpenes
    Language English
    Publishing date 2016-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 123545-x
    ISSN 1439-0221 ; 0032-0943
    ISSN (online) 1439-0221
    ISSN 0032-0943
    DOI 10.1055/s-0042-110575
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Liposomes Coloaded with Elacridar and Tariquidar To Modulate the P-Glycoprotein at the Blood-Brain Barrier.

    Nieto Montesinos, Rita / Béduneau, Arnaud / Lamprecht, Alf / Pellequer, Yann

    Molecular pharmaceutics

    2015  Volume 12, Issue 11, Page(s) 3829–3838

    Abstract: ... the P-glycoprotein-mediated efflux at the blood-brain barrier. Their pharmacokinetics, brain ... distribution, and impact on the model P-glycoprotein substrate, loperamide, were compared ... tariquidar by 1.4- and 2.1-fold, respectively, in comparison to both free P-gp modulators. Consequently ...

    Abstract This study prepared three liposomal formulations coloaded with elacridar and tariquidar to overcome the P-glycoprotein-mediated efflux at the blood-brain barrier. Their pharmacokinetics, brain distribution, and impact on the model P-glycoprotein substrate, loperamide, were compared to those for the coadministration of free elacridar plus free tariquidar. After intravenous administration in rats, elacridar and tariquidar in conventional liposomes were rapidly cleared from the bloodstream. Their low levels in the brain did not improve the loperamide brain distribution. Although elacridar and tariquidar in PEGylated liposomes exhibited 2.6 and 1.9 longer half-lives than free elacridar and free tariquidar, respectively, neither their Kp for the brain nor the loperamide brain distribution was improved. However, the conjugation of OX26 F(ab')2 fragments to PEGylated liposomes increased the Kps for the brain of elacridar and tariquidar by 1.4- and 2.1-fold, respectively, in comparison to both free P-gp modulators. Consequently, the Kp for the brain of loperamide increased by 2.7-fold. Moreover, the plasma pharmacokinetic parameters and liver distribution of loperamide were not modified by the PEGylated OX26 F(ab')2 immunoliposomes. Thus, this formulation represents a promising tool for modulating the P-glycoprotein-mediated efflux at the blood-brain barrier and could improve the brain uptake of any P-glycoprotein substrate that is intended to treat central nervous system diseases.
    MeSH term(s) ATP Binding Cassette Transporter, Sub-Family B/antagonists & inhibitors ; ATP Binding Cassette Transporter, Sub-Family B/metabolism ; Acridines/administration & dosage ; Acridines/pharmacokinetics ; Acridines/pharmacology ; Animals ; Antidiarrheals/pharmacokinetics ; Antidiarrheals/pharmacology ; Biological Transport ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/metabolism ; Brain/drug effects ; Brain/metabolism ; Chromatography, Liquid ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Gene Expression Regulation/drug effects ; Liposomes ; Loperamide/pharmacokinetics ; Loperamide/pharmacology ; Male ; Quinolines/administration & dosage ; Quinolines/pharmacokinetics ; Quinolines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tetrahydroisoquinolines/administration & dosage ; Tetrahydroisoquinolines/pharmacokinetics ; Tetrahydroisoquinolines/pharmacology ; Tissue Distribution
    Chemical Substances ATP Binding Cassette Transporter, Sub-Family B ; Acridines ; Antidiarrheals ; Liposomes ; Quinolines ; Tetrahydroisoquinolines ; Loperamide (6X9OC3H4II) ; tariquidar (J58862DTVD) ; Elacridar (N488540F94)
    Language English
    Publishing date 2015-11-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.5b00002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: GeneFisher-P: variations of GeneFisher as processes in Bio-jETI.

    Lamprecht, Anna-Lena / Margaria, Tiziana / Steffen, Bernhard / Sczyrba, Alexander / Hartmeier, Sven / Giegerich, Robert

    BMC bioinformatics

    2008  Volume 9 Suppl 4, Page(s) S13

    Abstract: ... techniques. We apply a service-oriented approach to model and implement GeneFisher-P, a process-based version ... The resulting service- and process-oriented GeneFisher-P demonstrates how basic services from heterogeneous ...

    Abstract Background: PCR primer design is an everyday, but not trivial task requiring state-of-the-art software. We describe the popular tool GeneFisher and explain its recent restructuring using workflow techniques. We apply a service-oriented approach to model and implement GeneFisher-P, a process-based version of the GeneFisher web application, as a part of the Bio-jETI platform for service modeling and execution. We show how to introduce a flexible process layer to meet the growing demand for improved user-friendliness and flexibility.
    Results: Within Bio-jETI, we model the process using the jABC framework, a mature model-driven, service-oriented process definition platform. We encapsulate remote legacy tools and integrate web services using jETI, an extension of the jABC for seamless integration of remote resources as basic services, ready to be used in the process. Some of the basic services used by GeneFisher are in fact already provided as individual web services at BiBiServ and can be directly accessed. Others are legacy programs, and are made available to Bio-jETI via the jETI technology. The full power of service-based process orientation is required when more bioinformatics tools, available as web services or via jETI, lead to easy extensions or variations of the basic process. This concerns for instance variations of data retrieval or alignment tools as provided by the European Bioinformatics Institute (EBI).
    Conclusions: The resulting service- and process-oriented GeneFisher-P demonstrates how basic services from heterogeneous sources can be easily orchestrated in the Bio-jETI platform and lead to a flexible family of specialized processes tailored to specific tasks.
    MeSH term(s) Algorithms ; Base Sequence ; DNA Primers/genetics ; Gene Targeting/methods ; Molecular Sequence Data ; Polymerase Chain Reaction/methods ; Sequence Alignment/methods ; Sequence Analysis, DNA/methods ; Software
    Chemical Substances DNA Primers
    Language English
    Publishing date 2008-04-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041484-5
    ISSN 1471-2105 ; 1471-2105
    ISSN (online) 1471-2105
    ISSN 1471-2105
    DOI 10.1186/1471-2105-9-S4-S13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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