Synthesis of N‐tert ‐butyl‐α‐(4‐[ 18 F]fluorophenyl)‐nitrone ([ 18 F]FPBN) for in vivo detection of free radicals

We have synthesized the fluorine‐18 labeled derivative of N ‐ tert ‐butyl‐α‐phenylnitrone (PBN), a free radical spin trapping agent widely used with electron spin resonance (ESR). N ‐ tert ‐Butyl‐α‐(4‐[ 18 F]fluorophenyl)‐nitrone ([ 18 F]FPBN) could be prepared with low radiochemical yield (3% decay corrected) by the direct aromatic nucleophilic substitution of N ‐ tert ‐butyl‐α‐(4‐nitrophenyl)nitrone with [ 18 F]fluoride. An alternate two step synthesis route consisted of the nucleophilic [ 18 F]fluoride substitution of 4‐ N , N , N ‐trimethylammoniumbenzaldehyde triflate to yield 4‐[ 18 F]fluorobenzaldehyde, which was distilled into a vial containing N ‐ tert ‐butyl‐hydroxylamine in 2N NaOH. 4‐[ 18 F]Fluorobenzaldehyde readily reacted with the hydroxylamine to form [ 18 F]FPBN. [ 18 F]FPBN was obtained in overall decay corrected yields of 24% in a total synthesis time < 45 min. and was suitable for further applications in in vivo studies of free radicals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90158/1/2580360202_ftp.pd

Synthesis, Biodistribution and In vitro Evaluation of Brain Permeable High Affinity Type 2 Cannabinoid Receptor Agonists [11C]MA2 and [18F]MA3

Abstract The type 2 cannabinoid receptor (CB2) is a member of the endocannabinoid system and is known for its important role in (neuro)inflammation. A PET-imaging agent that allows in vivo visualization of CB2 expression may thus allow quantification of neuroinflammation. In this paper, we report the synthesis, radiosynthesis, biodistribution and in vitro evaluation of a carbon-11 ([11C]MA2) and a fluorine-18 ([18F]MA3) labeled analogue of a highly potent N-arylamide oxadiazole CB2 agonist (EC50 = 0.015 nM). MA2 and MA3 behaved as potent CB2 agonist (EC50: 3 nM and 0.1 nM, respectively) and their in vitro binding affinity for hCB2 was found to be 87 nM and 0.8 nM, respectively. Also MA3 (substituted with a fluoro ethyl group) was found to have higher binding affinity and EC50 values when compared to the originally reported trifluoromethyl analogue 12. [11C]MA2 and [18F]MA3 were successfully synthesized with good radiochemical yield, high radiochemical purity and high specific activity. In mice, both tracers were efficiently cleared from blood and all major organs by the hepatobiliary pathway and importantly these compounds showed high brain uptake. In conclusion, [11C]MA2 and [18F]MA3 are shown to be high potent CB2 agonists with good brain uptake, these favorable characteristics makes them potential PET probes for in vivo imaging of brain CB2 receptors. However in view of its higher affinity and selectivity, further detailed evaluation of MA3 as a PET tracer for CB2 is warranted

Thermal study of the effect of several solvents on polymerization of acrylonitrile and their subsequent pyrolysis

The polymerization of acrylonitrile to polyacrylonitrile (PAN) has been studied using several solvents: N,N-dimethylformamide (DMF), hexane, toluene, water, and in bulk form (no solvent). The addition of DMF is the only case where both monomer and polymer are soluble in the solvent. Thermal analyses of the resultant products after polymerization have been performed by differential scanning calorimetry and pyrolysis–gas chromatography: mass spectrometry. The effect of the solvents employed as media for polymerization is interpreted from the results of the thermal and structural (X-ray diffraction) methods. The polymer samples obtained when using water or toluene as solvents have the greater content of amorphous components compared to the others. The amide molecules are difficult to completely eliminate in the product obtained after the polymerization reaction and even after prolonged heating at 110°C and remain occluded. DMF can be considered to exert a plasticized effect on PAN and is even capable of forming complexes by dipolar bonding. As a result of this interaction, the thermogram is quite different from the other samples studied in the present work, showing a single sharp exothermic peak. This is associated with nitrile group polymerization (cyclization) of PAN. It is deduced that the amount of heat evolved as well as the temperature interval over which it is released are influenced by the chemical processing of PAN, in particular when using DMF as solvent for both monomer and polymer. Pyrolysis of the different PAN samples revealed the release of occluded solvent molecules, mainly when using DMF, and compounds produced from the thermal degradation processes. Different types of cyclized compounds, such as pyridine derivatives and aromatic nitriles were identified. All these compounds could be derived from cyclized PAN structures which are not completely degraded by the thermal treatment of pyrolysis. Alkyldinitriles have also been tentatively identified associated with the final molecular breakdown of cyclized structures with six-member rings by pyrolysis. Valuable complementary information on the structure of the PAN samples (homopolymer) obtained using the different processing approaches involving several solvent media has been provided by pyrolysis. The present results will improve our understanding of the evolution of the structure and properties of carbon and activated carbon fibres which will enable us to establish processing strategies in order to obtain these materials under adequate and reproducible conditions.Peer reviewe

Artificial mixing to control cyanobacterial blooms: a review

Artificial mixing has been used as a measure to prevent the growth of cyanobacteria in eutrophic lakes and reservoirs for many years. In this paper, we give an overview of studies that report on the results of this remedy. Generally, artificial mixing causes an increase in the oxygen content of the water, an increase in the temperature in the deep layers but a decrease in the upper layers, while the standing crop of phytoplankton (i.e. the chlorophyll content per m2) often increases partly due to an increase in nutrients entrained from the hypolimnion or resuspended from the sediments. A change in composition from cyanobacterial dominance to green algae and diatoms can be observed if the imposed mixing is strong enough to keep the cyanobacteria entrained in the turbulent flow, the mixing is deep enough to limit light availability and the mixing devices are well distributed horizontally over the lake. Both models and experimental studies show that if phytoplankton is entrained in the turbulent flow and redistributed vertically over the entire depth, green algae and diatoms win the competition over (colonial) cyanobacteria due to a higher growth rate and reduced sedimentation losses. The advantage of buoyant cyanobacteria to float up to the illuminated upper layers is eradicated in a well-mixed system

Two-layer rotating exchange flow between two deep basins : theory and application to the Strait of Gibraltar

Author Posting. © American Meteorological Society, 2005. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 35 (2005): 1568–1592, doi:10.1175/JPO2775.1.Rotating two-layer exchange flow over a sill in a strait separating two relatively deep and wide basins is analyzed. Upstream of the sill in the deep upstream basin, the infinitely deep dense lower layer is assumed to be inactive, while the relatively thin upper layer flowing away from the sill forms a detached boundary current in the upstream basin. This analysis emphasizes the importance of this upstream boundary current, incorporating its width as a key parameter in a formalism for deducing the volume exchange rate and discriminating between maximal and submaximal states. Hence, even for narrow straits in which rotation does not dominate the dynamics within the strait, the importance of rotation in the wide upstream basin can be exploited. It is shown that the maximal allowable exchange transport through straits wider than 1½ Rossby deformation radii increases as rotation increases, unlike for smaller rotations, where the exchange decreases as rotation increases. The theory is applied to the exchange flow through the Strait of Gibraltar. This application illustrates how images of the oceans taken from space showing the width of the upstream flow, in this case a space shuttle photograph, might be used to determine the exchange transport through a strait. Maximal exchange conditions in the Strait of Gibraltar are predicted to apply at the time the space shuttle photograph was taken

Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

OBJECTIVES: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN: Prospective cohort study. SETTING: A total of 306 ICUs from 24 European countries. PARTICIPANTS: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male). MEASUREMENTS: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die. CONCLUSION: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity

Development and biological evaluation of 99mTc-sulfonamide derivatives for in? vivo visualization of CA IX as surrogate tumor hypoxia markers

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