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Visar resultat 1 - 5 av 34 avhandlingar som matchar ovanstående sökkriterier.

  1. 1. Development of Methods for Assessing Unbound Drug Exposure in the Brain : In vivo, in vitro and in silico

    Författare :Markus Fridén; Margareta Hammarlund-Udenaes; Ulf Bredberg; Yuichi Sugiyama; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Blood-brain barrier; Drug transport; Tissue distribution; Transporters; Pharmacokinetics; Other pharmacy; Övrig farmaci; Biopharmacy; Biofarmaci; Pharmaceutical pharmacology; Farmaceutisk farmakologi; Pharmacokinetics and Drug Therapy; Farmakokinetik och läkemedelsterapi;

    Sammanfattning : The blood-brain barrier is formed by tightly joined capillary cells with transporter proteins and acts as to regulate the brain concentration of nutrients as well as many drugs. When developing central nervous system drugs it is necessary to measure the unbound drug concentration in the brain, i.e. the unbound brain exposure. LÄS MER

  2. 2. Improving alternatives assessment of plastic additives : exploring in silico tools to identify less hazardous flame retardants

    Författare :Ziye Zheng; Patrik L. Andersson; Hans Peter Arp; Gregory Peters; Gerrit Schüürmann; Umeå universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; NATURVETENSKAP; NATURAL SCIENCES; Chemical alternatives assessment; plastic additives; flame retardants; hazard; emission; in silico; modeling; quantitative structure-activity relationship QSAR ; multi-criteria decision analysis MCDA ; environmental science; miljövetenskap; organisk kemi; Organic Chemistry; ekotoxikologi; Ecotoxicology; Toxicology; toxikologi;

    Sammanfattning : Alternatives assessment is applied for replacing hazardous chemicals with viable, safer substitutes. High quality experimental hazard data, however, are usually unavailable for this purpose, and obtaining in silico data is the only approach to fill in data gaps. LÄS MER

  3. 3. In vitro and in silico Predictions of Hepatic Transporter-Mediated Drug Clearance and Drug-Drug Interactions in vivo

    Författare :Anna Vildhede; Per Artursson; Maria Karlgren; Maria Kjellsson; Ulf Norinder; Kim Brouwer; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; OATP1B1; OATP1B3; OATP2B1; NTCP; drug transporters; human hepatocytes; atorvastatin; pitavastatin; proteomics; sandwich-cultured human hepatocytes; SCHH; mechanistic modeling; in vitro-in vivo extrapolation; transport inhibition; hepatic uptake; hepatocyte isolation; transporter contribution; Biopharmaceutics; Biofarmaci;

    Sammanfattning : The liver is the major detoxifying organ, clearing the blood from drugs and other xenobiotics. The extent of hepatic clearance (CL) determines drug exposure and hence, the efficacy and toxicity associated with exposure. Drug-drug interactions (DDIs) that alter the hepatic CL may cause more or less severe outcomes, such as adverse drug reactions. LÄS MER

  4. 4. In silico Identification of Thyroid Disrupting Chemicals : among industrial chemicals and household dust contaminants

    Författare :Jin Zhang; Patrik Andersson; A. Elisabeth Sauer-Eriksson; Liang-Hong Guo; Umeå universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Thyroid disruption chemicals; virtual screening; tranthyretin; thyroid hormone receptor; QSAR modeling; molecular docking; molecular dynamics;

    Sammanfattning : Thyroid disruptions by xenobiotics have been associated with a broad spectrum of severe adverse human health effects, such as impaired brain development and metabolic syndrome. Ingestion of indoor dust and contact with industrial chemicals are two significant human exposure routes of thyroid hormone disrupting chemicals (THDCs), raising serious concerns for human health. LÄS MER

  5. 5. Modeling Biochemical Network Involved in Striatal Dopamine Signaling

    Författare :Anu G. Nair; Jeanette Hellgren Kotaleski; Omar Gutierrez Arenas; Upinder Singh Bhalla; Jakob Kisbye Dreyer; KTH; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Dopamine signaling; Striatum; Reward learning; Acetylcholine; Mass-action modeling; FRET biosensor; Adenosine; Eligibility trace; Computer Science; Datalogi;

    Sammanfattning : In this thesis, I studied the molecular integration of reward-learning related neuromodulatory inputs by striatal medium-sized projection neurons (MSNs) using mass-action kinetic modeling.It is known that, in reward learning, an unexpected reward results in transient elevation in dopamine (peak) whereas omission of an expected reward leads to transient dopamine decrease (dip). LÄS MER