8-Bicycloalkyl-CPFPX derivatives as potent and selective tools for in vivo imaging of the A adenosine receptor.

Imaging of the A adenosine receptor (AR) by positron emission tomography (PET) with 8-cyclopentyl-3-(3-[F]fluoropropyl)-1-propyl-xanthine ([F]CPFPX) has been widely used in preclinical and clinical studies. However, this radioligand suffers from rapid peripheral metabolism and subsequent accumulation of radiometabolites in the vascular compartment. In the present work, we prepared four derivatives of CPFPX by replacement of the cyclopentyl group with norbornane moieties.

Radiosynthesis and In Vitro Evaluation of [C]tozadenant as Adenosine A Receptor Radioligand.

Tozadenant (4-hydroxy--(4-methoxy-7-morpholinobenzo[]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A receptor (AR) antagonist and a promising lead structure for the development of AR-selective positron emission tomography (PET) probes. Although several F-labelled tozadenant derivatives showed favorable in vitro properties, recent in vivo PET studies observed poor brain penetration and lower specific binding than anticipated from the in vitro data. While these findings might be attributable to the structural modification associated with F-labelling, they could also reflect inherent properties of the parent compound.

Association of Gabapentinoids With Opioid-Related Overdose in the Inpatient Setting: A Single Center Retrospective Case-Control Study.

Recent data suggest concomitant gabapentinoid use increases opioid-related overdose (ORO) risk; however, this association has not been well studied in the hospital setting. The primary objective of this study was to compare ORO risk, indicated by naloxone administration, in patients receiving opioids plus gabapentinoids versus opioids alone. In this retrospective case-control study of adults admitted to a large community hospital from 1/1/20 to 12/31/21, all cases (defined as patients who received naloxone more than 24 hours after admission) identified were matched 1:1 to randomly selected controls (defined as patients on opioids who did not receive naloxone).

Validation of analytical HPLC with post-column injection as a method for rapid and precise quantification of radiochemical yields.

Accurate assessment of isolated radiochemical yields (RCYs) is a prerequisite for efficient and reliable optimization of labeling reactions. In practice, radiochemical conversions (RCCs) determined by HPLC analysis of crude reaction mixtures are often used to estimate RCYs. However, incomplete recovery of radioactivity from the stationary phase can lead to significant inaccuracies if RCCs are calculated based on the activity eluted from the column (i.

7-[F]Fluoro-8-azaisatoic Anhydrides: Versatile Prosthetic Groups for the Preparation of PET Tracers.

F-Fluorination of sensitive molecules is often challenging, but can be accomplished under suitably mild conditions using radiofluorinated prosthetic groups (PGs). Herein, 1-alkylamino-7-[F]fluoro-8-azaisatoic anhydrides ([F]AFAs) are introduced as versatile F-labeled building blocks that can be used as amine-reactive or "click chemistry" PGs. [F]AFAs were efficiently prepared within 15 min by "on cartridge" radiolabeling of readily accessible trimethylammonium precursors.

Quetiapine and olanzapine misuse prevalence in a US general population sample.

Introduction: Second-generation antipsychotics (SGA) are associated with misuse potential; however, there are limited data describing the prevalence and characteristics of this misuse. This study was conducted to identify and describe quetiapine and olanzapine misuse among US adults.

Methods: This cross-sectional survey questionnaire was conducted online using Qualtrics research panel aggregator service to identify a quota-based sample of respondents constructed to mimic the general US population aged 18 to 59 years, with regards to gender, geographic region, ethnicity, income, and education level.

Evaluation of the F-labeled analog of the therapeutic all-D-enantiomeric peptide RD2 for amyloid β imaging.

Positron emission tomography (PET) imaging with radiotracers that bind to fibrillary amyloid β (Aβ) deposits is an important tool for the diagnosis of Alzheimer's disease (AD) and for the recruitment of patients into clinical trials. However, it has been suggested that rather than the fibrillary Aβ deposits, it is smaller, soluble Aβ aggregates that exert a neurotoxic effect and trigger AD pathogenesis. The aim of the current study is to develop a PET probe that is capable of detecting small aggregates and soluble Aβ oligomers for improved diagnosis and therapy monitoring.

Community pharmacists' counseling regarding nicotine replacement therapy: A secret shopper study.

Background: Nicotine replacement therapy (NRT) is a safe and effective non-prescription tobacco cessation treatment. While most community-based pharmacists periodically provide patient education regarding NRT, there is a gap in real-world evidence assessing the counseling provided.

Objectives: To assess community pharmacist counseling regarding NRT in a real-world setting.

[F]ALX5406: A Brain-Penetrating Prodrug for GlyT1-Specific PET Imaging.

Selective inhibition of glycine transporter 1 (GlyT1) has emerged as a potential approach to alleviate -methyl-d-aspartate receptor (NMDAR) hypofunction in patients with schizophrenia and cognitive decline. ALX5407 is a potent and selective inhibitor of GlyT1 derived from the metabolic intermediate sarcosine (-methylglycine) that showed antipsychotic potential in a number of animal models. Whereas clinical application of ALX5407 is limited by adverse effects on motor performance and respiratory function, a suitably radiolabeled drug could represent a promising PET tracer for the visualization of GlyT1 in the brain.

Rapid F-labeling via Pd-catalyzed S-arylation in aqueous medium.

We report radiolabeling of thiol-containing substrates via Pd-catalyzed S-arylation with 2-[F]fluoro-5-iodopyridine, which is readily accessible using the "minimalist" radiofluorination method. The practicality of the procedure was confirmed by preparation of a novel PSMA-specific PET-tracer as well as labeling of glutathione, Aβ oligomer-binding RD2 peptide, bovine serum albumin and PSMA I&S.

Baeyer-Villiger oxidation tuned to chemoselective conversion of non-activated [ F]fluorobenzaldehydes to [ F]fluorophenols.

A reaction pathway via oxidation of [ F]fluorobenzaldehydes offers a very useful tool for the no-carrier-added radiosynthesis of [ F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer-Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2-trifluoroethanol as reaction solvent in combination with Oxone or m-CPBA as oxidation agent. The studies showed the necessity of H SO addition, which appears to have a dual effect, acting as catalyst and desiccant.

Ultrasound-Guided Electrodes for Conduction Studies of the Saphenous Nerve.

Purpose: Saphenous nerve conduction studies are difficult, because the nerve is hard to localize and evoked responses are small. Ultrasound imaging may assist in the accurate localization and optimal positioning of surface (SE) and needle electrodes (NE).

Methods: The study population included 39 subjects and was divided into two groups.

No-carrier-added labeling of the neuroprotective Ebselen with selenium-73 and selenium-75.

Selenium-73 is a positron emitting non-standard radionuclide, which is suitable for positron emission tomography. A copper-catalyzed reaction allowed no-carrier-added labeling of the anti-inflammatory seleno-organic compound Ebselen with (73) Se and (75) Se under addition of sulfur carrier in a one-step reaction. The new authentically labeled radioselenium molecule is thus available for preclinical evaluation and positron emission tomography studies.

Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial.

Background: Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects.

Objectives: To report the 12-month extension of a phase II trial evaluating the efficacy, safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b) in relapsing-remitting multiple sclerosis (RRMS).

Methods: In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b.

Tolerance of intravenous methylprednisolone for relapse treatment in demyelinating CNS disease.

Background: In Switzerland, the first course of intravenous steroids for treatment of episodes of demyelinating CNS disease is usually administered in an inpatient setting. We prospectively evaluated short term tolerance of treatment with special emphasis on sleep quality.

Methods: Patients with a first event of presumed demyelinating disease (CIS), multiple sclerosis relapses (MS) or sub-acute disease progression were treated with a 5-day regimen of intravenous methylprednisolone (IVMP) in our inpatient clinic.

Atorvastatin added to interferon β for relapsing multiple sclerosis: a randomized controlled trial.

Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day.

Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls.

Background: In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role.

Objective: The objective of this study was to analyse the central motor conduction changes in relation to muscle contraction force during muscle fatigue and recovery in MS patients compared to healthy controls.

Campylobacter jejuni abscess, encephalomyelitis, and acute polyradiculoneuropathy.

We report an unusual case of spinal epidural Campylobacter jejuni abscess associated with acute polyradiculoneuropathy and parainfectious encephalomyelitis. Decompressive surgery, antibiotics, intravenous immunoglobulin (IVIg) therapy, and intravenous methylprednisolone resulted in rapid clinical improvement. C.