starMC: an automata based CTL* model checker.

Model-checking of temporal logic formulae is a widely used technique for the verification of systems. CTL is a temporal logic that allows to consider an intermix of both branching behaviours (like in CTL) and linear behaviours (LTL), overcoming the limitations of LTL (that cannot express "possibility") and CTL (cannot fully express fairness). Nevertheless CTL model-checkers are uncommon.

Pharmacokinetic properties of enantiomerically pure GluN2B selective NMDA receptor antagonists with 3-benzazepine scaffold.

Recently, the eutomers of highly potent GluN2B selective NMDA receptor antagonists with 3-benzazepine scaffold were identified. Herein, pharmacokinetic properties regarding lipophilicity, plasma protein binding (PPB) and metabolism are analyzed. The logD values of 1.

Design, (Radio)Synthesis, and in Vitro and in Vivo Evaluation of Highly Selective and Potent Matrix Metalloproteinase 12 (MMP-12) Inhibitors as Radiotracers for Positron Emission Tomography.

Dysregulated levels of activated matrix metalloproteinases (MMPs) are linked to different pathologies, such as cancer, atherosclerosis, neuroinflammation, and arthritis. Therefore, imaging of MMPs with positron-emission tomography (PET) represents a powerful tool for the diagnosis of MMP-associated diseases. Moreover, to distinguish between the distinct functions and roles of individual MMPs in particular pathophysiological processes, their specific imaging must be realized with radiolabeled tracers, such as fluorine-18-labeled MMP inhibitors (MMPIs).

Georg Schmorl Prize of the German Spine Society (DWG) 2017: correction of spino-pelvic alignment with relordosing mono- and bisegmental TLIF spondylodesis.

Introduction: A balanced ratio of the main parameters of lumbar lordosis (LL) and pelvic incidence (PI) has high clinical relevance. A postoperative mismatch of LL and PI has been described in the literature to be associated with an inferior clinical outcome and higher postoperative revision rates. The aim of this retrospective, radiological study is to evaluate the magnitude of relordosing in mono-/bisegmental TLIF spondylodesis affecting the spino-pelvic alignment and the main contributing factors.

Comparison of in Silico, Electrochemical, in Vitro and in Vivo Metabolism of a Homologous Series of (Radio)fluorinated σ Receptor Ligands Designed for Positron Emission Tomography.

The imaging of σ receptors in the brain by fluorinated radiotracers will be used for the validation of σ receptors as drug targets as well as for differential diagnosis of diseases in the central nervous system. The biotransformation of four homologous fluorinated PET tracers 1'-benzyl-3-(ω-fluoromethyl to ω-fluorobutyl)-3H-spiro[2]benzofuran-1,4'-piperidine] ([ F]1-4) was investigated. In silico studies using fast metabolizer (FAME) software, electrochemical oxidations, in vitro studies with rat liver microsomes, and in vivo metabolism studies after application of the PET tracers [ F]1-4 to mice were performed.

Radiolabeled hydroxamate-based matrix metalloproteinase inhibitors: How chemical modifications affect pharmacokinetics and metabolic stability.

Introduction: Dysregulated MMP expression or activation is associated with several diseases. To study MMP activity in vivo by means of PET a radiolabeled MMP inhibitor (MMPI) functioning as radiotracer has been developed by our group based on the lead structure CGS 25966.

Materials And Methods: Aiming at the modification of the pharmacokinetics of this lipophilic model tracer a new class of MMPIs has been discovered, consisting of additional fluorinated hydrophilic substructures, such as mini-PEG and/or 1,2,3-triazole units.

Synthesis and pharmacological evaluation of 5-pyrrolidinylquinoxalines as a novel class of peripherally restricted κ-opioid receptor agonists.

5-Pyrrolidinyl substituted perhydroquinoxalines were designed as conformationally restricted κ-opioid receptor agonists restricted to the periphery. The additional N atom of the quinoxaline system located outside the ethylenediamine κ pharmacophore allows the fine-tuning of the pharmacodynamic and pharmacokinetic properties. The perhydroquinoxalines were synthesized stereoselectively using the concept of late stage diversification of the central building blocks 14.

Hydroxyalkylation with cyclic sulfates: synthesis of carbazole derived CB(2) ligands with increased polarity.

In order to increase the polarity of the potent CB2 ligand 1a, the homologous hydroxyalkyl carbazoles 2a-c were prepared and pharmacologically evaluated. An important step in the synthesis is the hydroxyalkylation of carbazole with cyclic sulfates providing the 2-hydroxyethyl and 3-hydroxypropyl derivatives 5a and 5b in a one-step reaction. The final propionamides 2a-c were prepared using the recently reported coupling reagent COMU®.

Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone.

Background: Treatment of herpes zoster (HZ) includes the use of acyclovir with or without steroids. An alternative therapy is the epidural administration of local anesthetics with or without steroids. This trial compared the efficacy of these two treatment regimens in the prevention of post-herpetic neuralgia (PHN).

Blood concentrations and clinical effect of cyclosporin in psoriasis.

After approval by the Local Ethical Committee, 60 psoriatic patients, who participated in a previous pharmacokinetic study on cyclosporin A (CsA), gave their informed consent to continue to be studied during the maintenance treatment and at withdrawal. Peak concentration (Cmax), area under the concentration-time curve (AUC), bioavailability, elimination half-life, distribution volume, and body clearance were determined at monthly check-ups, along with blood pressure, psoriasis area, severity index (PASI), and creatinine serum levels. No modifications over time of treatment were observed on kinetic parameters.

Cyclosporin nephrotoxicity in relation to its metabolism in psoriasis.

Cyclosporine (CsA) and some of its metabolites (M9, M17, M18, M21) have been determined by means of an LC-MASS method in eight psoriatic patients developing nephrotoxicity. In comparison with a control group (15 psoriatics who after the same period of time, with the same daily dose, did not develop nephrotoxicity) they showed an increase of CsA metabolites, especially M17. Because M17 blood concentrations in the nephrotoxic group tended to be higher than in the control group from the first week of treatment we suggest that M17 might be considered a marker of ongoing nephrotoxicity.

Oral and intravenous disposition of cyclosporine in psoriatic patients.

After informed consent was obtained and with the approval of the Local Ethical Committee, cyclosporine A (CsA) kinetics was studied in 63 psoriatic patients by giving them 2.5 mg/kg CsA orally. In order to calculate oral bioavailability, F, 22 patients were given the same dose i.