Browsing by Subject "Heparin"

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  • Runeberg-Roos, Pia; Piccinini, Elisa; Penttinen, Anna-Maija; Matlik, Kert; Heikkinen, Hanna; Kuure, Satu; Bespalov, Maxim M.; Peranen, Johan; Garea-Rodriguez, Enrique; Fuchs, Eberhard; Airavaara, Mikko; Kalkkinen, Nisse; Penn, Richard; Saarma, Mart (2016)
    In Parkinson's disease midbrain dopaminergic neurons degenerate and die. Oral medications and deep brain stimulation can relieve the initial symptoms, but the disease continues to progress. Growth factors that might support the survival, enhance the activity, or even regenerate degenerating dopamine neurons have been tried with mixed results in patients. As growth factors do not pass the blood-brain barrier, they have to be delivered intracranially. Therefore their efficient diffusion in brain tissue is of crucial importance. To improve the diffusion of the growth factor neurturin (NRTN), we modified its capacity to attach to heparan sulfates in the extracellular matrix. We present four new, biologically fully active variants with reduced heparin binding. Two of these variants are more stable than WT NRTN in vitro and diffuse better in rat brains. We also show that one of the NRTN variants diffuses better than its close homolog GDNF in monkey brains. The variant with the highest stability and widest diffusion regenerates dopamine fibers and improves the conditions of rats in a 6-hydroxydopamine model of Parkinson's disease more potently than GDNF, which previously showed modest efficacy in clinical trials. The new NRTN variants may help solve the major problem of inadequate distribution of NRTN in human brain tissue. (C) 2016 Elsevier Inc. All rights reserved.
  • Tverring, Jonas; Vaara, Suvi T.; Fisher, Jane; Poukkanen, Meri; Pettila, Ville; Linder, Adam; FINNAKI Study Grp (2017)
    Background: Sepsis-related acute kidney injury (AKI) accounts for major morbidity and mortality among the critically ill. Heparin-binding protein (HBP)is a promising biomarker in predicting development and prognosis of severe sepsis and septic shock that has recently been proposed to be involved in the pathophysiology of AKI. The objective of this study was to investigate the added predictive value of measuring plasma HBP on admission to the intensive care unit (ICU) regarding the development of septic AKI. Methods: We included 601 patients with severe sepsis or septic shock from the prospective, observational FINNAKI study conducted in seventeen Finnish ICUs during a 5-month period (1 September 2011-1 February 2012). The main outcome measure was the development of KDIGO AKI stages 2-3 from 12 h after admission up to 5 days. Statistical analysis for the primary endpoint included construction of a clinical risk model, area under the receiver operating curve (ROC area), category-free net reclassification index (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence intervals (95% CI). Results: Out of 511 eligible patients, 101 (20%) reached the primary endpoint. The addition of plasma HBP to a clinical risk model significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk classification scores: cfNRI 62.0% (95% CI 40.5-82.4%) and IDI 0.053 (95% CI 0.029-0.075). Conclusions: Plasma HBP adds predictive value to known clinical risk factors in septic AKI. Further studies are warranted to compare the predictive performance of plasma HBP to other novel AKI biomarkers.
  • Tirri, Tomi (Helsingin yliopisto, 2017)
    Kuvantamista hyödyntävässä toimenpiteessä eli toimenpideradiologiassa on kliininen tarve määrittää potilaan tukos- tai vuototaipumusta. Ultraäänitoimenpiteissä vuotoriskiä ennakoidaan protrombiiniajan (PT) ja siitä johdetun International Ration (INR) avulla. Sydänpotilailla tukosriskiä pienennetään toimenpiteen aikana annostelemalla suonen- sisäisesti hepariinia, jolloin aktivoidulla hyytymisajalla (ACT) voidaan seurata hepariinin vaikutusta. Kannettavalla vierilaitteella voidaan verianalyysit suorittaa toimenpide- huoneessa,jolloin tulosviive pienenee. Tutkielmassa verifioitiin HUS-Kuvantamisen radiologian hankkima ITC Hemochron® Signature Elite-vierilaitteen kokoverianalyysit PT, INR ja aktivoitu partielli tromboplastiiniaika (APTT) vertaamalla laitteen antamia tuloksia laboratorion veriplasmaa käyttäviin analyysituloksiin. Laitteen aktivoidun hyytymisajan (ACT LR ja ACT+) tuloksia verrattiin laboratorion antifaktori X-aktiivisuuteen (anti-FXa). Tavoitteena oli selvittää potilasaineiston avulla soveltuuko ITC Hemochron® Signature Elite-vierilaite kliiniseen käyttöön toimenpideradiologiassa. Ultraäänitoimenpiteissä potilaita oli yhteensä 20 ja sydänpotilaita oli 15. Potilaita ei valikoitu vaan kaikki näyt- teiden keräyspäivinä tammikuussa ja huhtikuussa 2015 HUS-Kuvantaminen radiolo- giassa ulträäni- tai sydäntoimenpiteissä olleet potilaat otettiin mukaan. PT-mittauksissa ero laboratorion menetelmän ja Hemochron® Signature Elite PT:n välillä oli -5,5 sekuntia (-26,3 prosenttia) ja keskinäinen riippuvuus eli korrelaatio vähäinen (R=0,02). INR- mittauksissa ero oli 0,15 (15 prosenttia) ja korrelaatio vähäinen (R=0,1). APTT-mittauk- sissa ero oli 8,4 sekuntia (33,9 prosenttia) ja korrelaatio alhainen (R=0,33). ACT LR:lle ja ACT+:lle ei määritelty eroa, koska mittausasteikko eroaa laboratorion antiFXa:n kanssa. ACT LR:lle saatii korrelaatio oli 0,49 ja ja ACT+:lle 0,35.
  • Vahtera, Annukka; Valkonen, Miia; Huhtala, Heini; Pettila, Ville; Kuitunen, Anne (2017)
    Introduction: In intensive care unit (ICU) patients, subcutaneous low-molecular weight heparin thromboprophylaxis results in lower plasma anti-factor Xa (anti-FXa) levels compared to general ward patients. The aim of this study was to examine whether enoxaparin thromboprophylaxis given as a continuous intravenous infusion (CII) results in more constant and predictable anti-FXa concentration than standard subcutaneous bolus (SCB) administration. Materials and methods: This was a prospective, single-blind, multicenter, randomized controlled trial where ICU patients requiring thromboprophylaxis received enoxaparin either 40 mg as a SCB once daily or 40 mg as a CII over 24 h for three consecutive days. The primary outcome was maximum serum anti-FXa concentration (C-max24 (h)) within the first 24 h; the secondary outcome was anti-FXa area under the curve (AUC)((0-24 h)). Trough level was measured at 72 h. Results: Thirty-nine patients were included in the intention to treat analysis. The median anti-FXa C-max24 (h) was 0.05 (interquartile range, IQR, 0.05-0.18) IU/ml in the CII group and 0.18 (IQR, 0.12-0.33) IU/ml in the SCB group (p= 0.05). Median anti-FXa AUC((0-24 h)) was 1.20 (IQR, 0.98-2.88) in the CII and 1.54 (IQR, 1.22-4.12) in the SCB group (p = 0.095). After 72 h, 66.7% of patients in the CII group had a detectable anti-FXa concentration of > 0.1 IU/ml, compared with 16.7% in the SCB group (p = 0.019). Conclusions: Continuous infusion of enoxaparin led to lower anti-FXa C-max24 h than standard SCB administration. No difference in anti-FXa AUC(0-24) (h) was detected.
  • Galambosi, Päivi; Ulander, Veli-Matti; Kaaja, Risto (2018)