Organic Cation Transporter-Mediated Accumulation of Quinolinium Salts in the LV Myocardium of Rodents.

Purpose: Quaternary ammonium salts have demonstrated marked accumulation in the left ventricular (LV) myocardium of rodents and swine. To investigate the mechanism underlying this uptake, the present study examined the interaction of [F]fluoroethylquinolinium ([F]FEtQ) with the family of organic cation transporters (OCTs).

Procedures: The cellular uptake of [F]FEtQ into HEK293 cells, expressing human OCT1, -2, or -3 (HEK293-hOCT), and its inhibition by corticosterone was evaluated in vitro.

Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging.

We previously presented the radiolabeled ammonium salt [C]-dimethyl diphenylammonium trifluoromethanesulfonate ([C]DMDPA) as a potential novel PET-MPI agent. The current study aimed to increase the clinical applicability of PET-MPI by designing and synthesizing fluorinated ammonium salt derivatives. Four fluorinated DMDPA derivatives and two quinolinium salt analogs were radiolabeled.

MiR-21-5p but not miR-1-3p expression is modulated by preconditioning in a rat model of myocardial infarction.

Isoflurane (Iso) preconditioning (PC) is known to be cardioprotective against ischemia/reperfusion (I/R) injury. It was previously shown that microRNA-21-5p (miR-21-5p) is regulated by Iso-PC. It is unclear, if expression of cardiac enriched miR-1-3p is also affected by Iso-PC, and associated with activation of HIF1α (hypoxia-inducible factor 1-alpha).

Fine-tuning of the automated [ F]PSMA-1007 radiosynthesis.

Radiolabeled prostate-specific membrane antigen (PSMA) targeting PET-tracers have become desirable radiopharmaceuticals for the imaging of prostate cancer (PC). Recently, the PET radiotracer [ F]PSMA-1007 was introduced as an alternative to [ Ga]Ga-PSMA-11, for staging and diagnosing biochemically recurrent PC. We incorporated a one-step procedure for [ F]PSMA-1007 radiosynthesis, using both Synthra RNplus and GE TRACERlab FxFN automated modules, in accordance with the recently described radiolabeling procedure.

Sevoflurane postconditioning is not mediated by ferritin accumulation and cannot be rescued by simvastatin in isolated streptozotocin-induced diabetic rat hearts.

Sevoflurane postconditioning (sevo postC) is an attractive and amenable approach that can protect the myocardium against ischemia/reperfusion (I/R)-injury. Unlike ischemic preconditioning (IPC), sevo postC does not require additional induced ischemic periods to a heart that is already at risk. IPC was previously shown to generate myocardial protection against I/R-injury through regulation of iron homeostasis and de novo ferritin synthesis, a process found to be impaired in the diabetic state.

Development of a Fluorinated Analogue of Erlotinib for PET Imaging of EGFR Mutation-Positive NSCLC.

Purpose: Positron emission tomography (PET) using [C]erlotinib identifies non-small cell lung carcinoma (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR). The short half-life of C-11, however, limits its clinical utility to centers with a nearby cyclotron. We therefore developed a F-18-labeled analogue of erlotinib for imaging EGFR NSCLC.

Protection by Nitric Oxide Donors of Isolated Rat Hearts Is Associated with Activation of Redox Metabolism and Ferritin Accumulation.

Preconditioning (PC) procedures (ischemic or pharmacological) are powerful procedures used for attaining protection against prolonged ischemia and reperfusion (I/R) injury, in a variety of organs, including the heart. The detailed molecular mechanisms underlying the protection by PC are however, complex and only partially understood. Recently, an 'iron-based mechanism' (IBM), that includes de novo ferritin synthesis and accumulation, was proposed to explain the specific steps in cardioprotection generated by IPC.

Morphine-Induced Preconditioning: Involvement of Protein Kinase A and Mitochondrial Permeability Transition Pore.

Background: Morphine induces myocardial preconditioning (M-PC) via activation of mitochondrial large conductance Ca2+-sensitive potassium (mKCa) channels. An upstream regulator of mKCa channels is protein kinase A (PKA). Furthermore, mKCa channel activation regulates mitochondrial bioenergetics and thereby prevents opening of the mitochondrial permeability transition pore (mPTP).

Effects of remote ischemic preconditioning and myocardial ischemia on microRNA-1 expression in the rat heart in vivo.

Remote ischemic preconditioning (RIPC) is an easily applicable method for protecting the heart against a subsequent ischemia and reperfusion (I/R) injury. However, the exact molecular mechanisms underlying RIPC are unknown. We examined the involvement of microRNAs (miRNAs) and in particular the expression of miRNA-1 (miR-1) in RIPC and myocardial ischemia.

Expression of spinal cord microRNAs in a rat model of chronic neuropathic pain.

Neuropathic pain is accompanied by significant alterations of gene expression patterns in the somatosensory nervous system. The spinal cord is particularly prone to neuroplastic changes. Since the expression of microRNAs (miRNAs) has been linked to numerous pathophysiological processes, a contribution of miRNAs to the maladaptive plasticity of the spinal cord in neuropathic pain is possible.

Allele-specific differences in ryanodine receptor 1 mRNA expression levels may contribute to phenotypic variability in malignant hyperthermia.

Background: Malignant hyperthermia (MH) is a dominantly inherited skeletal muscle disorder that can cause a fatal hypermetabolic reaction to general anaesthetics. The primary locus of MH (MHS1 locus) in humans is linked to chromosome 19q13.1, the position of the gene encoding the ryanodine receptor skeletal muscle calcium release channel (RyR1).

Identification of ryanodine receptor 1 single-nucleotide polymorphisms by high-resolution melting using the LightCycler 480 System.

High-resolution melting (HRM) allows single-nucleotide polymorphism (SNP) detection/typing using inexpensive generic heteroduplex-detecting double-stranded DNA (dsDNA) binding dyes. Until recently HRM has been a post-PCR process. With the LightCycler 480 System, however, the entire mutation screening process, including post-PCR analysis, can be performed using a single instrument.