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  1. Artikel ; Online: Individualized Protease Inhibitor Monotherapy: The Role of Pharmacokinetics and Pharmacogenetics in an Aged and Heavily Treated HIV-Infected Patient.

    López Aspiroz, Elena / Cabrera Figueroa, Salvador Enrique / Valverde Merino, María Paz / Carracedo Álvarez, Ángel

    Clinical drug investigation

    2019  Band 39, Heft 11, Seite(n) 1125–1131

    Abstract: Antiretroviral therapy has changed the history of HIV infection from a lethal disease to a chronic infection, with the emergence of long-term adverse effects. Herein we present a case of a heavily treated HIV-infected man in whom antiretroviral toxicity ... ...

    Abstract Antiretroviral therapy has changed the history of HIV infection from a lethal disease to a chronic infection, with the emergence of long-term adverse effects. Herein we present a case of a heavily treated HIV-infected man in whom antiretroviral toxicity had been observed. The lopinavir/ritonavir plasma concentrations at standard doses were significantly above the recommended levels. Pharmacogenetic analysis revealed a polymorphism in the DRD3 gene associated with a decrease in the rate of drug metabolism. Additionally, the patient's low body mass index could have contributed to a greater degree of patient exposure to the drug. After the withdrawal of tenofovir disoproxil and the establishment of individualized protease inhibitor monotherapy at reduced doses, a decrease in the intensity of adverse events was observed, while the clinical outcomes were maintained. The pharmacokinetic-pharmacogenetic analysis was shown to be a tool of huge interest for the management and durability of antiretroviral therapy.
    Mesh-Begriff(e) Age Factors ; Drug Substitution/methods ; HIV Infections/drug therapy ; HIV Infections/genetics ; HIV Infections/metabolism ; HIV Protease Inhibitors/adverse effects ; HIV Protease Inhibitors/pharmacokinetics ; HIV-1/drug effects ; HIV-1/genetics ; Humans ; Male ; Middle Aged ; Pharmacogenetics/methods ; Precision Medicine/methods ; Treatment Outcome
    Chemische Substanzen HIV Protease Inhibitors
    Sprache Englisch
    Erscheinungsdatum 2019-08-07
    Erscheinungsland New Zealand
    Dokumenttyp Case Reports ; Journal Article
    ZDB-ID 1220136-4
    ISSN 1179-1918 ; 0114-2402 ; 1173-2563
    ISSN (online) 1179-1918
    ISSN 0114-2402 ; 1173-2563
    DOI 10.1007/s40261-019-00829-x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution.

    Mosquera Orgueira, Adrián / Antelo Rodríguez, Beatriz / Alonso Vence, Natalia / Díaz Arias, José Ángel / Díaz Varela, Nicolás / Pérez Encinas, Manuel Mateo / Allegue Toscano, Catarina / Goiricelaya Seco, Elena María / Carracedo Álvarez, Ángel / Bello López, José Luis

    BMC cancer

    2019  Band 19, Heft 1, Seite(n) 515

    Abstract: Background: Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad ... ...

    Abstract Background: Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad of somatic events driving CLL proliferation and aggressivity. Nevertheless, and despite the mounting evidence of inherited risk for CLL development, the existence of germline variants associated with clinical outcomes has not been addressed in depth.
    Methods: Exome sequencing data from control leukocytes of CLL patients involved in the International Cancer Genome Consortium (ICGC) was used for genotyping. Cox regression was used to detect variants associated with clinical outcomes. Gene and pathways level associations were also calculated.
    Results: Single nucleotide polymorphisms in PPP4R2 and MAP3K4 were associated with earlier treatment need. A gene-level analysis evidenced a significant association of RIPK3 with both treatment need and survival. Furthermore, germline variability in pathways such as apoptosis, cell-cycle, pentose phosphate, GNα13 and Nitric oxide was associated with overall survival.
    Conclusion: Our results support the existence of inherited conditionants of CLL evolution and points towards genes and pathways that may results useful as biomarkers of disease outcome. More research is needed to validate these findings.
    Mesh-Begriff(e) Biomarkers, Tumor/genetics ; Female ; GTP-Binding Protein alpha Subunits, G12-G13/genetics ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; MAP Kinase Kinase Kinase 4/genetics ; Male ; Phosphoprotein Phosphatases/genetics ; Survival Analysis ; Whole Exome Sequencing/methods
    Chemische Substanzen Biomarkers, Tumor ; GNA13 protein, human ; MAP Kinase Kinase Kinase 4 (EC 2.7.11.25) ; MAP3K4 protein, human (EC 2.7.11.25) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; protein phosphatase 4 (EC 3.1.3.16) ; GTP-Binding Protein alpha Subunits, G12-G13 (EC 3.6.5.1)
    Sprache Englisch
    Erscheinungsdatum 2019-05-29
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 1471-2407
    ISSN (online) 1471-2407
    DOI 10.1186/s12885-019-5628-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Impact of pharmacogenetics on CNS side effects related to efavirenz.

    Sánchez Martín, Almudena / Cabrera Figueroa, Salvador / Cruz Guerrero, Raquel / Hurtado, Liliana Porras / Hurlé, Alfonso Dominguez-Gil / Carracedo Álvarez, Angel

    Pharmacogenomics

    2013  Band 14, Heft 10, Seite(n) 1167–1178

    Abstract: Aim: This article evaluates which genetic factors are involved in CNS toxicity related to long-term treatment with efavirenz (EFV) standard doses and their relationship with plasma concentrations.: Patients & methods: A total of 119 HIV-positive ... ...

    Abstract Aim: This article evaluates which genetic factors are involved in CNS toxicity related to long-term treatment with efavirenz (EFV) standard doses and their relationship with plasma concentrations.
    Patients & methods: A total of 119 HIV-positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 EFV-related adverse effects (AEs) were analyzed.
    Results: Overall, 32.77% of patients reported CNS toxicity and 8.40% had concentrations above the therapeutic range. A correlation was mainly found between patients with global CNS AEs and high EFV maximum steady-state plasma concentration (p = 1.47 × 10(-6)). A preliminary analysis confirmed that CYP2B6*6 (516G>T and 785A>G) was the most highly correlated (p = 0.005) with AEs and high plasma concentrations. In a second analysis adjusting for maximum steady-state plasma concentration, suggestive genetic associations were found between BCRP 421C>A, MRP1 816G>A, 5-HT2A 102C>T and different AEs.
    Conclusion: The finding of the involvement of these SNPs in EFV toxicity opens the door for further studies to confirm their validity and for their application in the future clinical practice. Original submitted 18 February 2013; Revision submitted 17 May 2013.
    Mesh-Begriff(e) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-HIV Agents/administration & dosage ; Anti-HIV Agents/adverse effects ; Aryl Hydrocarbon Hydroxylases/genetics ; Benzoxazines/administration & dosage ; Benzoxazines/adverse effects ; Benzoxazines/pharmacokinetics ; Biomarkers, Pharmacological ; Central Nervous System Diseases/chemically induced ; Central Nervous System Diseases/genetics ; Cytochrome P-450 CYP2B6 ; Female ; HIV/pathogenicity ; HIV Infections/drug therapy ; HIV Infections/genetics ; Humans ; Male ; Middle Aged ; Pharmacogenetics ; Polymorphism, Single Nucleotide
    Chemische Substanzen Anti-HIV Agents ; Benzoxazines ; Biomarkers, Pharmacological ; Aryl Hydrocarbon Hydroxylases (EC 1.14.14.1) ; CYP2B6 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP2B6 (EC 1.14.14.1) ; efavirenz (JE6H2O27P8)
    Sprache Englisch
    Erscheinungsdatum 2013-07
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs.13.111
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 5247: Hefte anzeigen Standort:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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