Automated Solid-Phase Radiofluorination Using Polymer-Supported Phosphazenes

The polymer supported phosphazene bases PS-P2tBu and the novel PS-P2PEG allowed for efficient extraction of [18F]F− from proton irradiated [18O]H2O and subsequent radiofluorination of a broad range of substrates directly on the resin. The highest radiochemical yields were obtained with aliphatic sulfonates (69%) and bromides (42%); the total radiosynthesis time was 35–45 min. The multivariate analysis showed that the radiochemical yields and purities were controlled by the resin load, reaction temperature, and column packing effects. The resins could be reused several times with the same or different substrates. The fully automated on-column radiofluorination methodology was applied to the radiosynthesis of the important PET radiotracers [18F]FLT and [18F]FDG. The latter was produced with 40% yield on a 120 GBq scale and passed GMP-regulated quality control required for commercial production of [18F]FDG. The combination of compact form factor, simplicity of [18F]F− recovery and processing, and column reusability can make solid phase radiofluorination an attractive radiochemistry platform for the emerging dose-on-demand instruments for bedside production of PET radiotracers

Urteekstrakter som bæredygtigt bekæmpelsesmiddel mod parasitter i økologisk fiskeopdræt

Opdræt af regnbueørred, særligt økologisk ørred, er udfordret på grund af gælle- og hudparasitinfektioner forårsaget af en række forskellige patogener. Det drejer sig især om mikroskopiske flagellater, fimredyr samt en række amøber. Da flere andre typer parasitter er følsomme over for indholdsstoffer i hvidløg, oregano og timian kunne ekstrakter fra disse krydderurter måske være en del af løsningen også for dambrugsfisk. Vore laboratorieforsøg viste, at fiskeparasitter faktisk var følsomme over for et eller flere indholdsstoffer i hvidløg, oregano og timian. Men det viste sig også, at det kun var timian og en biologisk sæbe fra bakterien Pseudomonas, som blev veltolereret af fiskene, mens ekstrakter af oregano og hvidløg ikke blev vel modtaget af regnbueørrederne. Timian-ekstrakt havde således antiparasitisk effekt, idet snylterne på fiskens hud døde og løsnedes fra både hud, finner og gæller. En andet stof, isoleret fra Pseudomonas H6 bakterien, som er en biologisk sæbe (en surfaktant, et overfladeaktivt molekyle), viste sig også at være effektiv mod flere typer parasitter

Towards automated solid phase radiofluorination for dose-on-demand PET: retention of activity by solid support

On-column [18F]fluoride trapping and radiofluorination of 2-(naphthalen-1-yl)ethyl-4-methylbenzenesulfonate (C10H7(CH2)2OTs), performed on polystyrene supported phosphazene base PS-PtBu2 yielded [18F]1-(2-fluoroethyl)naphthalene ([18F]C10H7(CH2)2F) in 50% radiochemical yield but left up to 43% of activity unreacted on the resin. This activity could be eluted with Kryptofix/K2CO3 and then used for conventional radiofluorination of the same substrate, suggesting that the column-retained activity was present in the form of [18F]fluoride entrapped in polymer matrix. An approach to minimize the amount of entrapped [18F]fluoride by use of glass beads functionalized with alkylsilane-derivatized phosphazene residues was attempted but was stymied by fluorolysis/hydrolysis of the alkylsilane spacer. The results suggest that the key to high yield of on-column radiofluorination is to minimize the residual [18F]fluoride absorption in the matrix by the judicious choice of solid support

A non-lethal method for detection of <i>Bonamia ostreae</i> in flat oyster (<i>Ostrea edulis</i>) using environmental DNA

Surveillance and diagnosis of parasitic Bonamia ostreae infections in flat oysters (Ostrea edulis) are prerequisites for protection and management of wild populations. In addition, reliable and non-lethal detection methods are required for selection of healthy brood oysters in aquaculture productions. Here we present a non-lethal diagnostic technique based on environmental DNA (eDNA) from water samples and demonstrate applications in laboratory trials. Forty oysters originating from Limfjorden, Denmark were kept in 30 ppt sea water in individual tanks. Water was sampled 6 days later, after which all oysters were euthanized and examined for infection, applying PCR. Four oysters (10%) were found to be infected with B. ostreae in gill and mantle tissue. eDNA purified from the water surrounding these oysters contained parasite DNA. A subsequent sampling from the field encompassed 20 oysters and 15 water samples from 5 different locations. Only one oyster turned out positive and all water samples proved negative for B. ostreae eDNA. With this new method B. ostreae may be detected by only sampling water from the environment of isolated oysters or isolated oyster populations. This non-lethal diagnostic eDNA method could have potential for future surveys and oyster breeding programs aiming at producing disease-free oysters.publishedVersio

Biomarkers of cardiovascular risk across phenotypes of osteoarthritis.

BACKGROUND: The objective of this study was to explore the associations between ultrasonographic and radiographic joint scores and levels of arterial CVD risk markers in patients with osteoarthritis (OA). Secondly, to compare the levels of arterial CVD risk markers between OA phenotypes and controls. METHOD: The "Musculoskeletal pain in Ullensaker" Study (MUST) invited residents of Ullensaker municipality with self-reported OA to a medical examination. OA was defined according to the American College of Rheumatology (ACR) criteria and phenotyped based on joint distribution. Joints of the hands, hips and knees were examined by ultrasonography and conventional radiography, and scored for osteosteophytes. Hands were also scored for inflammation by grey scale (GS) synovitis and power Doppler (PD) signal. Control populations were a cohort of inhabitants of Oslo (OCP), and for external validation, a UK community-based register (UKPC).Pulse pressure augmentation index (AIx) and pulse wave velocity (PWV) were measured using the Sphygmocor apparatus (Atcor®). Ankel-brachial index (ABI) was estimated in a subset of patients. In separate adjusted regression models we explored the associations between ultrasonography and radiograph joint scores and AIx, PWV and ABI. CVD risk markers were also compared between phenotypes of OA and controls in adjusted analyses. RESULTS: Three hundred and sixty six persons with OA were included (mean age (range); 63.0 (42.0-75.0)), (females (%); 264 (72)). Of these, 155 (42.3%) had isolated hand OA, 111 (30.3%) had isolated lower limb OA and 100 (27.3%) had generalized OA. 108 persons were included in the OCP and 963 persons in the UKPC; (mean age (range); OCP: 57.2 (40.4-70.4), UKPC: 63.9 (40.0-75.0), females (%); OCP: 47 (43.5), UKPC: 543 (56.4%). Hand osteophytes were associated with AIx while GS and PD scores were not related to CVD risk markers. All OA phenotypes had higher levels of AIx compared to OCP in adjusted analyses. External validation against UKPC confirmed these findings. CONCLUSIONS: Hand osteophytes might be related to higher risk of CVD. People with OA had higher augmented central pressure compared to controls.Words 330

Comparative In Vitro and In Vivo Effects of Feed Additives on Rainbow Trout Response to Ichthyophthirius multifiliis

Control of the skin parasitic ciliate Ichthyophthirius multifiliis is currently based on laborious chemical and mechanical approaches, thus advocating for alternative control measures. Here, we show that the early development of trophonts (feeding stage residing in the epidermis) in the Rainbow Trout Oncorhynchus mykiss epidermis was inhib-ited at 5 d postinfection after the administration of feed additives, including garlic Allium sativum, oregano Origanum onites, thyme Thymus vulgaris, coriander Coriandrum sativum, and astaxanthin (a carotenoid derived from the alga Haematococcus pluvialis). However, no inhibition was observed at 8 d postinfection. We investigated whether the early inhibition was caused by (1) the feed additives’ direct effect on the parasite and/or (2) stimulation of the Rainbow Trout immune responses. Garlic exhibited the highest in vitro killing capacity toward theronts (the infective stage of the parasite), followed by oregano, thyme, and astaxanthin, whereas coriander had no in vitro parasiticidal effect. Immune reactions were measured by plasma lysozyme activity in Rainbow Trout after feeding and by recording immune gene expression in trout leukocytes that were exposed to feed additives. Oregano-fed fish showed a signifi-cantly (P < 0.05) elevated plasma lysozyme activity. Oregano and thyme—and to a lesser extent, garlic, astaxanthin, and coriander—induced a significant regulation of innate and adaptive immune genes in vitro. The results suggest that the investigated additives inhibit early parasite development directly as well as indirectly (i.e., by elevating the host immune response)

Biomarkers of cardiovascular risk across phenotypes of osteoarthritis

Abstract: Background: The objective of this study was to explore the associations between ultrasonographic and radiographic joint scores and levels of arterial CVD risk markers in patients with osteoarthritis (OA). Secondly, to compare the levels of arterial CVD risk markers between OA phenotypes and controls. Method: The “Musculoskeletal pain in Ullensaker” Study (MUST) invited residents of Ullensaker municipality with self-reported OA to a medical examination. OA was defined according to the American College of Rheumatology (ACR) criteria and phenotyped based on joint distribution. Joints of the hands, hips and knees were examined by ultrasonography and conventional radiography, and scored for osteosteophytes. Hands were also scored for inflammation by grey scale (GS) synovitis and power Doppler (PD) signal. Control populations were a cohort of inhabitants of Oslo (OCP), and for external validation, a UK community-based register (UKPC). Pulse pressure augmentation index (AIx) and pulse wave velocity (PWV) were measured using the Sphygmocor apparatus (Atcor®). Ankel-brachial index (ABI) was estimated in a subset of patients. In separate adjusted regression models we explored the associations between ultrasonography and radiograph joint scores and AIx, PWV and ABI. CVD risk markers were also compared between phenotypes of OA and controls in adjusted analyses. Results: Three hundred and sixty six persons with OA were included (mean age (range); 63.0 (42.0–75.0)), (females (%); 264 (72)). Of these, 155 (42.3%) had isolated hand OA, 111 (30.3%) had isolated lower limb OA and 100 (27.3%) had generalized OA. 108 persons were included in the OCP and 963 persons in the UKPC; (mean age (range); OCP: 57.2 (40.4–70.4), UKPC: 63.9 (40.0–75.0), females (%); OCP: 47 (43.5), UKPC: 543 (56.4%). Hand osteophytes were associated with AIx while GS and PD scores were not related to CVD risk markers. All OA phenotypes had higher levels of AIx compared to OCP in adjusted analyses. External validation against UKPC confirmed these findings. Conclusions: Hand osteophytes might be related to higher risk of CVD. People with OA had higher augmented central pressure compared to controls. Words 330