Joko olet tutustunut Lääkehoidon tietopaketteihin?

Fimean lääkehoidon tietopaketit tarjoavat konkreettisia työkaluja sosiaali- ja terveydenhuollon ammattilaisille. Lisäksi tietopaketit auttavat sosiaali- ja terveydenhuollon organisaatioita kehittämään järkevän lääkehoidon toteutumista edistäviä prosesseja. Tietopakettien sisältöä voi vapaasti hyödyntää omassa työssään tai vaikka koulutusmateriaalina toimipaikkakoulutuksissa. Niistä löytyy myös lääkkeiden käyttäjille suunnattua materiaalia. Tietopakettien tunnettuudesta ja käytettävyydestä toteutettiin kysely alkukesällä 2019. Tulosten pohjalta tietopaketteja on edelleen kehitetty

Disease-Modifying Antirheumatic Drugs and Risk of Parkinson Disease Nested Case-Control Study of People With Rheumatoid Arthritis

Background and Objectives Epidemiologic studies have suggested a link between rheumatoid arthritis and Parkinson disease (PD). Disease-modifying antirheumatic drugs (DMARDs) might explain this association. The aim of this work was to evaluate the association between DMARDs and risk of PD in persons with rheumatoid arthritis. Methods This nested nationwide case-control study was conducted within the Finnish Parkinson's Disease (FINPARK) cohort, which includes 22,189 Finnish persons with clinically verified PD diagnosed in 1996 to 2015. The cases had recorded diagnosis of PD in the Special Reimbursement Register and had no exclusion diagnoses with symptoms that may be confused with PD within 2 years of PD diagnosis. This study included cases with PD diagnosed during 1999 to 2015 and rheumatoid arthritis diagnosed >3 years before PD. Rheumatoid arthritis was identified from the Finnish Care Register for Health Care and Special Reimbursement Register. Cases were matched with up to 7 controls by age, sex, duration of rheumatoid arthritis, and region. DMARDs were categorized into 5 classes, and data on purchased prescriptions were identified from the Prescription Register since 1995. Associations were studied with conditional logistic regression adjusted for confounders. Results Altogether, 315 cases with PD and 1,571 matched controls were included. The majority (>60%) were women, and the median duration of rheumatoid arthritis on matching date was 11.6 years for controls and 12.6 years for cases. Use of DMARDs was not associated with risk of PD with a 3-year lag period applied between exposure and outcome except chloroquine/hydroxychloroquine, which associated with decreased risk (adjusted odds ratio [OR] 0.74, 95% confidence interval [CI] 0.56-0.97). Other DMARDs, including sulfasalazine, methotrexate, gold preparations, and immunosuppressants, were not associated with PD. Discussion Our results suggest that the lower risk of PD in people with rheumatoid arthritis is not explained by DMARD use because these drugs in general did not modify the risk of PD among persons with rheumatoid arthritis. Association between chloroquine/hydroxychloroquine and lower risk of PD and the possible underlying mechanisms should be further investigated. Classification of Evidence This study provides Class II evidence that in individuals with rheumatoid arthritis using DMARDs, only chloroquine/ hydroxychloroquine was associated with a potentially decreased risk of developing PD (adjusted OR 0.74, 95% CI 0.56-0.97).Peer reviewe

Epigenetic Upregulation of Endogenous VEGF-A Reduces Myocardial Infarct Size in Mice

<div><p>“Epigenetherapy” alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral <i>in vivo</i> delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of vascular endothelial growth factor (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and multiphoton microscope analysis confirmed the therapeutic effect in the transduced hearts. Magnetic resonance imaging (MRI) showed <i>in vivo</i> that the infarct size was significantly reduced in the treatment group 14 days after the epigenetherapy. Importantly, we show that promoter-targeted shRNA upregulates all isoforms of endogenous VEGF-A and that an intact hairpin structure is required for the shRNA activity. In conclusion, regulation of gene expression at the promoter level is a promising new treatment strategy for myocardial infarction and also potentially useful for the upregulation of other endogenous genes.</p></div

ELISA assay of myocardial infarction samples and analysis for single-stranded vectors for a mechanistical view.

<p>(a) ELISA analysis of VEGF-A protein from transduced hearts, (b) ELISA assay from growth medium of C166 cells transduced with LV-451 and corresponding single stranded vectors using MOI 10, 7 days time point. (c) RT-PCR analysis of VEGF-A mRNA levels. C166 cells were transduced with LV-451 and corresponding single stranded vectors using MOI 10, 11 days time point. (d) qChIP assay of C166 cells using antibodies against H3K4me2. Cells were transduced with LV-451 and corresponding single stranded vectors using MOI 10, 11 days timepoint. All results are shown as mean ± SD.</p

Multiphoton microscopy and histology analysis of myocardial infarction animals.

<p>(a) Multiphoton laser scanning microscopy (MPLSM) analysis of GFP expression in transduced mouse heart, (b) Immunohistological analysis of GFP expression in mouse heart, (c) antibody omitted control, (d and k) Massons Trichrome staining from mouse heart transduced with VEGF-A upregulating LV-451 and shRNA control, respectively, (e and l) insert from infarcted area of d and k, respectively, (h and o) insert from infarct borderzone (f, i, m, p) alpha-SMA staining of smooth muscle cells, arrows point to arteriols formed, (g, j, n, q) CD-31 staining of endothelial cells. Scale bars (a) 100 µm, (d and k) 2000 µm, (e, f, g, h, i, j, l, m, n, o, p, q) 200 µm.</p

MRI analysis of murine myocardial infarction.

<p>Infarct size in VEGF-A upregulated (shRNA) and in control (shRNA Control) groups measured using MRI (a), and representative examples of short axis cine images with outlined (red lines) infarcts in late diastole at days 4 and 14 in both shRNA and shRNA control animals (b).</p

Analysis for mechanism of action for promoter targeted shRNAs.

<p>(a) RT-PCR analysis for different VEGF-A isoforms. The expression levels for different isoforms were studied using primers specific to each isoform. Total VEGF-A protein level was measured with ELISA. (b) Reversing DNA methylation with 5-Azacytidine treatment induces responses in MS1 cells but erases responses in C166 cells. Cells were treated with 1 µM 5-Azacytidine, transduced with different vectors on day 3 and samples were collected on day 8. qRT-PCR analysis of VEGF-A and B-actin mRNA levels in MS1 cells and C166 cells. (c) qChIP assay in MS1 cells using antibody against H3K27me3. (d) The VEGF-A gene promoter in C166 cells was also analyzed for basal DNA methylation levels without 5-Azacytidine treatment using MeDIP. Cells were transduced with different vectors using MOI 10, 10 days timepoint. (e) RT-PCR analysis of VEGF-A mRNA levels after C166 cells were transfected with siRNA oligos. Results are calculated in reference to housekeeping gene ACTB and control oligo. (f) CBP-CREB interaction inhibitor (7.5 µM) abolishes the upregulation of VEGF-A by LV-451 in C166 cells. For all results, mean ± SD shown.</p

Intracellular distribution of LV-451 expressed RNA and VEGF-A mRNA in transduced cells.

<p>C166 cells were subjected to RNA-FISH analysis with LV-451 or VEGF mRNA probes. (a) Confocal microscopy images of LV-451 transduced (MOI 10) cells 72 h post transduction. Distribution of LV-451 RNA (green) and VEGF-A mRNA (red) probe binding induced signals is shown. Nuclei were visualized with DAPI (grey). Scale bars, 5 µm. (b) Quantification of LV-451 RNA or VEGF-A mRNA RNA-FISH signal spots detected in LV-451 transduced (MOI 4, 40, 200) cells at 72 h post transduction and in nontransduced control cells. The amount of signal was calculated in the nucleus (white), the cytosol (grey) and whole cell (black). Error bars = SD. (c) Nucleus size in response to LV transduction. CTRL sample is nontransduced C166 cells and LV-451 is C166 cells transduced with LV-451 vector.</p