Failure to replicate? Exacerbated 8-OH-DPAT-induced hypothermia could not be established in single housed mice when tested as part of a battery of depression tests

We have previously described a depressive phenotype in male mice stemming from three weeks’ single housing, demonstrated as an exacerbated transient hypothermia following a challenge with the serotonin (5-HT) receptor agonist 8-OH-DPAT. In an attempt to flesh out the phenotype, we carried out a battery of tests used to assess depressive states on C57BL/6 mice of both sexes. When combining the 8-OH-DPAT challenge with the tail-suspension test, an open field test, a sucrose preference test, and blood samplings for measuring serum levels of oxytocin, we could find no clear evidence of depressive states in the single housed animals. The fact that we could not replicate our previous findings is puzzling; however, we suspect that the stressful nature of the test battery may have been detrimental to the model. These negative findings and their implications may prove of significant importance moving forward with studying natural models of depression

Effects of Transdermal Fentanyl Treatment on Acute Pain and Inflammation in Rats with Adjuvant-induced Monoarthritis

Eliminating unnecessary pain is an important requirement of performing animal experimentation, including reducing and controlling pain of animals used in pain research. The goal of this study was to refine an adjuvant-induced monoarthritis model in rats by providing analgesia with a transdermal fentanyl solution (TFS). Male and female Sprague-Dawley rats, single- or pair-housed, were injected with 20 μL of complete Freund adjuvant (CFA) into the left ankle joint. CFA-injected rats treated with a single dose of transdermal fentanyl solution (0.33 or 1 mg/kg) were compared with an untreated CFA-injected group and sham groups that received either no treatment or TFS treatment (1 mg/kg) during 72 h. At the tested doses, TFS reduced mechanical hyperalgesia and improved the mobility, stance, rearing, and lameness scores at 6 h after CFA injection. Joint circumferences were not reduced by TFS treatment, and no significant differences were detected between the 2 doses of TFS, or between single- and pair-housed rats. Treatment with TFS did not appear to interfere with model development and characteristics. However, overall, the analgesic effect was transient, and several opioid-related side effects were observed

Oncolytic Adenovirus Type 3 Coding for CD40L Facilitates Dendritic Cell Therapy of Prostate Cancer in Humanized Mice and Patient Samples

Dendritic cell (DC)-based vaccines have shown some degree of success for the treatment of prostate cancer (PC). However, the highly immunosuppressive tumor microenvironment leads to DC dysfunction, which has limited the effectiveness of these vaccines. We hypothesized that use of a fully serotype 3 oncolytic adenovirus (Ad3-hTERT-CMV-hCD40L; TILT-234) could stimulate DCs in the prostate tumor microenvironment by expressing CD40L. Activated DCs would then activate cytotoxic T cells against the tumor, resulting in therapeutic immune responses. Oncolytic cell killing due to cancer cell-specific virus replication adds to antitumor effects but also enhances the immunological effect by releasing tumor epitopes for sampling by DC, in the presence of danger signals. In this study, we evaluated the companion effect of Ad3-hTERT-CMV-hCD40L and DC-therapy in a humanized mouse model and PC histocultures. Treatment with Ad3-hTERT-CMV-hCD40L and DC resulted in enhanced antitumor responses in vivo. Treatment of established histocultures with Ad3-hTERT-CMV-hCD40L induced DC maturation and notable increase in proinflammatory cytokines. In conclusion, Ad3-hTERT-CMV-hCD40L is able to modulate an immunosuppressive prostate tumor microenvironment and improve the effectiveness of DC vaccination in PC models and patient histocultures, setting the stage for clinical translation.Peer reviewe

Kinetic analysis and optimisation of 18F-rhPSMA-7.3 PET imaging of prostate cancer

Purpose This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, F-18-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. Methods Nine men, three with high-risk localised prostate cancer, three with treatment-naive hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq F-18-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35-45, 60-88 and 90-118 min. Net influx rates (K-i) were calculated using Patlak plots.Results Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The F-18-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. K-i, SUV and lesion-to-reference ratio estimates showed good agreement. Conclusion F-18-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, F-18-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer.</p

Datan käsittelyyn tarkoitetun käyttöliittymän suunnittelu ja toteutus

Tässä opinnäytetyössä tarkasteltiin Googlen kehittämää Flutter-ohjelmistokehystä ja sen käyttöä verkkokehittämiseen. Flutter on visuaalinen ohjelmistokehys, joka on tarkoitettu tuomaan käyttöliittymän kehittämiseen tarkoitetut työkalut ja toiminnallisuudet. Flutter käyttää Googlen kehittämää Dart-ohjelmointikieltä. Flutter on jo melko laajalti käytetty mobiilikehityksessä, mutta ei ole saanut niin paljoa huomiota sen verkkosovellusten kehitykseen tehdyistä kirjastoista ja ominaisuuksista. Tässä opinnäytetyössä esitellään Flutter-ohjelmistokehyks ja sillä tehty verkkosovellus. Tämä verkkosovellus tuli käyttöön Oulun yliopistolle tukemaan siellä olevaa sensoriverkkoa ja antamaan tutkijoille ja opiskelijoille helpon pääsyn näiden sensoreiden tuottamaan dataan. Tämän opinnäytetyön keskeisin toteutustapa oli kehittämistyö. Tarkoituksena oli kehittää sovellus, joka tukee aiemmin tehtyä sensoriverkkoa ja antaa helpon tavan päästä käsiksi sen tuottamaan dataan. Flutter-ohjelmistokehystä on käsitelty aiemmin opinnäytetöissä, mutta ei niinkään verkkokehitykseen kohdistettuna. Tämän takia tärkeimpänä lähteenä ja aineistona toimikin Flutterin virallinen dokumentaatio. Tämä työ tehtiin AIF-tiimin alaisuudessa Oulun yliopistolla