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  1. Article ; Online: Perioperative Amiodarone to Prevent Atrial fibrillation after Septal Myectomy in obstrUctive hypeRtroPHic cardiomyopathy.

    Shalen, Evan F / Heitner, Stephen B / Al-Rashdan, Lana / Akhavein, Reyhaneh / Elman, Miriam R / Fischer, Katherine L / Lin, Lucy Q / Mannello, Meghan / Nazer, Babak / Song, Howard K / Masri, Ahmad

    ESC heart failure

    2021  Volume 8, Issue 6, Page(s) 4791–4799

    Abstract: Aims: Amiodarone reduces the incidence of atrial fibrillation (AF) following coronary artery bypass surgery; however, the benefit of perioperative amiodarone in patients undergoing septal myectomy (SM) for obstructive hypertrophic cardiomyopathy (oHCM) ... ...

    Abstract Aims: Amiodarone reduces the incidence of atrial fibrillation (AF) following coronary artery bypass surgery; however, the benefit of perioperative amiodarone in patients undergoing septal myectomy (SM) for obstructive hypertrophic cardiomyopathy (oHCM) has not been studied. We hypothesized that prophylactic amiodarone would reduce the incidence of postoperative AF (POAF) following SM for oHCM.
    Methods and results: A single-centre, pre-post intervention open-label study of oral amiodarone (200 mg twice daily starting 7 days preoperatively and 200 mg once daily continuing for 30 days postoperatively) in patients without prior AF undergoing SM for oHCM from 2014 to 2018. The primary outcome was incident AF within 30 days. Secondary outcomes were unplanned readmission, AF treatment, total and intensive care unit (ICU) length of stay (LOS), and pacemaker implantation for high-grade atrioventricular (AV) block. 61 patients met inclusion criteria with 34 (55.8%) in the pre-intervention (control) group and 27 (44.2%) in the post-intervention (amiodarone) group. The incidence of POAF was 11.0% in the amiodarone group compared with 38.2% in the control group (P = 0.017). After adjusting for age, amiodarone was associated with less POAF [adjusted odds ratio (aOR) 0.21; 95% confidence interval (CI) 0.05, 0.76; P = 0.016]. ICU (2 days [IQR 1, 4] vs. 3 days [IQR 2, 4]; P = 0.165) and total (6 days [IQR 5, 6] vs. 6 days [IQR 5, 7]; P = 0.165) LOS were similar, as was the rate of pacemaker implantation (7.4% vs. 8.3%, P > 0.999). There were no adverse events associated with amiodarone.
    Conclusions: Perioperative oral amiodarone is safe and was associated with lower incidence of POAF following SM for oHCM.
    MeSH term(s) Amiodarone/therapeutic use ; Atrial Fibrillation/epidemiology ; Atrial Fibrillation/etiology ; Atrial Fibrillation/prevention & control ; Cardiomyopathy, Hypertrophic/complications ; Coronary Artery Bypass/adverse effects ; Humans ; Length of Stay
    Chemical Substances Amiodarone (N3RQ532IUT)
    Language English
    Publishing date 2021-10-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2814355-3
    ISSN 2055-5822 ; 2055-5822
    ISSN (online) 2055-5822
    ISSN 2055-5822
    DOI 10.1002/ehf2.13662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Improved soluble expression and use of recombinant human renalase.

    Morrison, Clifford S / Paskaleva, Elena E / Rios, Marvin A / Beusse, Thomas R / Blair, Elaina M / Lin, Lucy Q / Hu, James R / Gorby, Aidan H / Dodds, David R / Armiger, William B / Dordick, Jonathan S / Koffas, Mattheos A G

    PloS one

    2020  Volume 15, Issue 11, Page(s) e0242109

    Abstract: Electrochemical bioreactor systems have enjoyed significant attention in the past few decades, particularly because of their applications to biobatteries, artificial photosynthetic systems, and microbial electrosynthesis. A key opportunity with ... ...

    Abstract Electrochemical bioreactor systems have enjoyed significant attention in the past few decades, particularly because of their applications to biobatteries, artificial photosynthetic systems, and microbial electrosynthesis. A key opportunity with electrochemical bioreactors is the ability to employ cofactor regeneration strategies critical in oxidative and reductive enzymatic and cell-based biotransformations. Electrochemical cofactor regeneration presents several advantages over other current cofactor regeneration systems, such as chemoenzymatic multi-enzyme reactions, because there is no need for a sacrificial substrate and a recycling enzyme. Additionally, process monitoring is simpler and downstream processing is less costly. However, the direct electrochemical reduction of NAD(P)+ on a cathode may produce adventitious side products, including isomers of NAD(P)H that can act as potent competitive inhibitors to NAD(P)H-requiring enzymes such as dehydrogenases. To overcome this limitation, we examined how nature addresses the adventitious formation of isomers of NAD(P)H. Specifically, renalases are enzymes that catalyze the oxidation of 1,2- and 1,6-NAD(P)H to NAD(P)+, yielding an effective recycling of unproductive NAD(P)H isomers. We designed several mutants of recombinant human renalase isoform 1 (rhRen1), expressed them in E. coli BL21(DE3) to enhance protein solubility, and evaluated the activity profiles of the renalase variants against NAD(P)H isomers. The potential for rhRen1 to be employed in engineering applications was then assessed in view of the enzyme's stability upon immobilization. Finally, comparative modeling was performed to assess the underlying reasons for the enhanced solubility and activity of the mutant enzymes.
    MeSH term(s) Enzyme Stability ; Escherichia coli ; Humans ; Industrial Microbiology/methods ; Monoamine Oxidase/chemistry ; Monoamine Oxidase/genetics ; Monoamine Oxidase/metabolism ; Mutation ; NADP/metabolism ; Protein Domains ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Solubility ; Static Electricity
    Chemical Substances Recombinant Proteins ; NADP (53-59-8) ; Monoamine Oxidase (EC 1.4.3.4) ; renalase (EC 1.4.3.4.)
    Language English
    Publishing date 2020-11-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0242109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Impact of Cardiovascular Magnetic Resonance Imaging on Identifying the Etiology of Cardiomyopathy in Patients Undergoing Cardiac Transplantation.

    Lin, Lucy Q / Kazmirczak, Felipe / Chen, Ko-Hsuan Amy / Okasha, Osama / Nijjar, Prabhjot S / Martin, Cindy M / Akçakaya, Mehmet / Farzaneh-Far, Afshin / Shenoy, Chetan

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 16212

    Abstract: Errors in identifying the etiology of cardiomyopathy have been described in patients undergoing cardiac transplantation. There are increasing data that cardiovascular magnetic resonance imaging (CMR) provides unique diagnostic information in heart ... ...

    Abstract Errors in identifying the etiology of cardiomyopathy have been described in patients undergoing cardiac transplantation. There are increasing data that cardiovascular magnetic resonance imaging (CMR) provides unique diagnostic information in heart failure. We investigated the association of the performance of CMR prior to cardiac transplantation with rates of errors in identifying the etiology of cardiomyopathy. We compared pre-transplantation clinical diagnoses with post-transplantation pathology diagnoses obtained from the explanted native hearts. Among 338 patients, there were 23 (7%) errors in identifying the etiology of cardiomyopathy. Of these, 22 (96%) occurred in patients with pre-transplantation clinical diagnoses of non-ischemic cardiomyopathy (NICM). Only 61/338 (18%) had CMRs prior to transplantation. There was no significant association between the performance of CMR and errors in the entire study cohort (p = 0.093). Among patients with pre-transplantation clinical diagnoses of NICM, there was a significant inverse association between the performance of CMR and errors (2.4% vs. 14.6% in patients with and without CMR respectively; p = 0.030). In conclusion, CMR was underutilized prior to cardiac transplantation. In patients with pre-transplantation clinical diagnoses of NICM - in whom 96% of errors in identifying the etiology of cardiomyopathy occurred - the performance of CMR was associated with significantly fewer errors.
    MeSH term(s) Adult ; Aged ; Biopsy ; Cardiomyopathies/diagnosis ; Cardiomyopathies/etiology ; Cardiomyopathies/therapy ; Echocardiography ; Female ; Heart Failure/diagnosis ; Heart Failure/etiology ; Heart Failure/therapy ; Heart Transplantation/adverse effects ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Retrospective Studies
    Language English
    Publishing date 2018-11-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-34648-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy.

    Kolishetti, Nagesh / Dhar, Shanta / Valencia, Pedro M / Lin, Lucy Q / Karnik, Rohit / Lippard, Stephen J / Langer, Robert / Farokhzad, Omid C

    Proceedings of the National Academy of Sciences of the United States of America

    2010  Volume 107, Issue 42, Page(s) 17939–17944

    Abstract: The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to ... ...

    Abstract The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to target and control precisely the codelivery of drugs with varying physicochemical properties to cancer cells. As proof of concept, we codelivered cisplatin and docetaxel (Dtxl) to prostate cancer cells with synergistic cytotoxicity. A polylactide (PLA) derivative with pendant hydroxyl groups was prepared and conjugated to a platinum(IV) [Pt(IV)] prodrug, c,t,c-[Pt(NH(3))(2)(O(2)CCH(2)CH(2)COOH)(OH)Cl(2)] [PLA-Pt(IV)]. A blend of PLA-Pt(IV) functionalized polymer and carboxyl-terminated poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) copolymer in the presence or absence of Dtxl, was converted, in microfluidic channels, to NPs with a diameter of ∼100 nm. This process resulted in excellent encapsulation efficiency (EE) and high loading of both hydrophilic platinum prodrug and hydrophobic Dtxl with reproducible EEs and loadings. The surface of the NPs was derivatized with the A10 aptamer, which binds to the prostate-specific membrane antigen (PSMA) on prostate cancer cells. These NPs undergo controlled release of both drugs over a period of 48-72 h. Targeted NPs were internalized by the PSMA-expressing LNCaP cells via endocytosis, and formation of cisplatin 1,2-d(GpG) intrastrand cross-links on nuclear DNA was verified. In vitro toxicities demonstrated superiority of the targeted dual-drug combination NPs over NPs with single drug or nontargeted NPs. This work reveals the potential of a single, programmable nanoparticle to blend and deliver a combination of drugs for cancer treatment.
    MeSH term(s) Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Cisplatin/administration & dosage ; Cisplatin/therapeutic use ; Docetaxel ; Drug Therapy, Combination ; Electrochemistry ; Endocytosis ; Humans ; Male ; Nanoparticles ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/pathology ; Taxoids/administration & dosage ; Taxoids/therapeutic use
    Chemical Substances Antineoplastic Agents ; Taxoids ; Docetaxel (15H5577CQD) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2010-10-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1011368107
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy

    Kolishetti, Nagesh / Dhar, Shanta / Valencia, Pedro M / Lin, Lucy Q / Karnik, Rohit / Lippard, Stephen J / Langer, Robert / Farokhzad, Omid C

    Proceedings of the National Academy of Sciences of the United States of America. 2010 Oct. 19, v. 107, no. 42

    2010  

    Abstract: The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to ... ...

    Abstract The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to target and control precisely the codelivery of drugs with varying physicochemical properties to cancer cells. As proof of concept, we codelivered cisplatin and docetaxel (Dtxl) to prostate cancer cells with synergistic cytotoxicity. A polylactide (PLA) derivative with pendant hydroxyl groups was prepared and conjugated to a platinum(IV) [Pt(IV)] prodrug, c,t,c-[Pt(NH₃)₂(O₂CCH₂CH₂COOH)(OH)Cl₂] [PLA-Pt(IV)]. A blend of PLA-Pt(IV) functionalized polymer and carboxyl-terminated poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) copolymer in the presence or absence of Dtxl, was converted, in microfluidic channels, to NPs with a diameter of ~100 nm. This process resulted in excellent encapsulation efficiency (EE) and high loading of both hydrophilic platinum prodrug and hydrophobic Dtxl with reproducible EEs and loadings. The surface of the NPs was derivatized with the A10 aptamer, which binds to the prostate-specific membrane antigen (PSMA) on prostate cancer cells. These NPs undergo controlled release of both drugs over a period of 48-72 h. Targeted NPs were internalized by the PSMA-expressing LNCaP cells via endocytosis, and formation of cisplatin 1,2-d(GpG) intrastrand cross-links on nuclear DNA was verified. In vitro toxicities demonstrated superiority of the targeted dual-drug combination NPs over NPs with single drug or nontargeted NPs. This work reveals the potential of a single, programmable nanoparticle to blend and deliver a combination of drugs for cancer treatment.
    Keywords ammonia ; antigens ; chlorine ; cisplatin ; combination drug therapy ; composite polymers ; crosslinking ; cytotoxicity ; encapsulation ; endocytosis ; engineering ; ethylene glycol ; hydrophilicity ; hydrophobicity ; mixing ; nanoparticles ; neoplasm cells ; nuclear genome ; oligonucleotides ; platinum ; polylactic acid ; prostatic neoplasms
    Language English
    Dates of publication 2010-1019
    Size p. 17939-17944.
    Publishing place National Academy of Sciences
    Document type Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1011368107
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy

    Kolishetti, Nagesh / Dhar, Shanta / Valencia, Pedro M. / Lin, Lucy Q. / Karnik, Rohit / Lippard, Stephen J. / Langer, Robert / Farokhzad, Omid C.
    Language English
    Document type Article
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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