An extra pair of eyes: adopting innovative approaches to detect integrity issues in Naunyn-Schmiedeberg's Archives of Pharmacology.

Scientific integrity has been increasingly challenged by scientific misconduct and paper mills, resulting in an increase in retractions. Naunyn-Schmiedeberg's Archives of Pharmacology has been significantly impacted by fraudulent submissions, resulting in numerous retractions. By analyzing retraction notes and utilizing a post-publication surveillance strategy, this editorial discusses how this journal continues to deal with problematic publications, uncovers image- and physiological-related integrity issues, and responds to fraudulent activity.

Analysis of drug-induced and spontaneous cardioversions reveals similar patterns leading to termination of atrial fibrillation.

Introduction: The mechanisms leading to the conversion of atrial fibrillation (AF) to sinus rhythm are poorly understood. This study describes the dynamic behavior of electrophysiological parameters and conduction patterns leading to spontaneous and pharmacological AF termination.

Methods: Five independent groups of goats were investigated: (1) spontaneous termination of AF, and drug-induced terminations of AF by various potassium channel inhibitors: (2) AP14145, (3) PA-6, (4) XAF-1407, and (5) vernakalant.

The network of cardiac K2.1: its function, cellular regulation, electrical signaling, diseases and new drug avenues.

The functioning of the human heart relies on complex electrical and communication systems that coordinate cardiac contractions and sustain rhythmicity. One of the key players contributing to this intricate system is the K2.1 potassium ion channel, which is encoded by the KCNJ2 gene.

Recording ten-fold larger I conductances with automated patch clamping using equimolar Cs solutions.

The rapid delayed rectifier potassium current (I) is important for cardiac repolarization and is most often involved in drug-induced arrhythmias. However, accurately measuring this current can be challenging in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes because of its small current density. Interestingly, the ion channel conducting I, hERG channel, is not only permeable to K ions but also to Cs ions when present in equimolar concentrations inside and outside of the cell.

The Utrecht University Honours Program review project: example based scientific publishing training aimed at bachelor medical students.

Introduction: Medical undergraduate students receive limited education on scholarly publishing. However, publishing experiences during this phase are known to influence study and career paths. The medical bachelor Honours Program (HP) at Utrecht University initiated a hands-on writing and publishing course, which resulted in nine reviews published in internationally peer reviewed academic journals.

High-rate pacing suppresses Torsade de Pointes arrhythmias and reduces spatial dispersion of repolarization in the chronic AV-block dog model.

An electrical storm of Torsade de Pointes arrhythmias (TdP) can be reproducibly induced in the anesthetized chronic AV-block (CAVB) dog by infusion of the I-blocker dofetilide. Earlier studies showed that these arrhythmias 1) arise from locations with high spatial dispersion in repolarization (SDR) and 2) can be suppressed by high-rate pacing. We examined whether suppression of TdP by high-rate pacing is established through a decrease in SDR in the CAVB dog.

Automatic measurement of short-term variability of repolarization to indicate ventricular arrhythmias in a porcine model of cardiac ischaemia.

Aims: An automated method for determination of short-term variability (STV) of repolarization on intracardiac electrograms (STV-ARIauto) has previously been developed for arrhythmic risk monitoring by cardiac implantable devices, and has proved effective in predicting ventricular arrhythmias (VA) and guiding preventive high-rate pacing (HRP) in a canine model. Current study aimed to assess (i) STV-ARIauto in relation to VA occurrence and secondarily (ii-a) to confirm the predictive capacity of STV from the QT interval and (ii-b) explore the effect of HRP on arrhythmic outcomes in a porcine model of acute myocardial infarction (MI).

Methods And Results: Myocardial infarction was induced in 15 pigs.

I Activator ML277 Mildly Affects Repolarization and Arrhythmic Outcome in the CAVB Dog Model.

Long QT syndrome type 1 with affected I is associated with a high risk for developing Torsade de Pointes (TdP) arrhythmias and eventually sudden cardiac death. Therefore, it is of high interest to explore drugs that target I as antiarrhythmics. We examined the antiarrhythmic effect of I channel activator ML277 in the chronic atrioventricular block (CAVB) dog model.

Chronic Propafenone Application Increases Functional K2.1 Expression In Vitro.

Expression and activity of inwardly rectifying potassium (K) channels within the heart are strictly regulated. K channels have an important role in shaping cardiac action potentials, having a limited conductance at depolarized potentials but contributing to the final stage of repolarization and resting membrane stability. Impaired K2.

Pro-Arrhythmic Potential of Accumulated Uremic Toxins Is Mediated via Vulnerability of Action Potential Repolarization.

Chronic kidney disease (CKD) is represented by a diminished filtration capacity of the kidneys. End-stage renal disease patients need dialysis treatment to remove waste and toxins from the circulation. However, endogenously produced uremic toxins (UTs) cannot always be filtered during dialysis.

Remodeling in the AV block dog is essential for tolerating moderate treadmill activity.

Background: A preclinical model standardized at different remodeling stages after AV block induction in awake state is suitable for the evaluation of improved cardiac devices. We studied exercise-induced cardiorespiratory parameters at three different timepoints after inducing AV block in dogs.

Methods: Mongrel dogs (n = 12) were placed on a treadmill with a 10% incline and performed a moderate exercise protocol (10-minute run at 6 km/h).

I inhibitor JNJ303 prolongs the QT interval and perpetuates arrhythmia when combined with enhanced inotropy in the CAVB dog.

Introduction: Impaired I induced by drugs or due to a KCNQ1 mutation, diagnosed as long QT syndrome type 1 (LQT1) prolongs the QT interval and predisposes the heart to Torsade de Pointes (TdP) arrhythmias. The anesthetized chronic AV block (CAVB) dog is inducible for TdP after remodeling and I inhibitor dofetilide. We tested the proarrhythmic effect of I inhibition in the CAVB dog, and the proarrhythmic role of increased contractility herein.

Quantitative Analysis of the Cytoskeleton's Role in Inward Rectifier K 2.1 Forward and Backward Trafficking.

Alteration of the inward rectifier current , carried by K2.1 channels, affects action potential duration, impacts resting membrane stability and associates with cardiac arrhythmias. Congenital and acquired K2.

Development of I Ion Channel Blockers Targeting Sulfonylurea Resistant Mutant K6.2 Based Channels for Treating DEND Syndrome.

DEND syndrome is a rare channelopathy characterized by a combination of developmental delay, epilepsy and severe neonatal diabetes. Gain of function mutations in the gene, encoding the K6.2 subunit of the I potassium channel, stand at the basis of most forms of DEND syndrome.

Does vitamin B12 deficiency explain psychiatric symptoms in recreational nitrous oxide users? A narrative review.

Recreational use of nitrous oxide (NO) is associated with many side effects, of which neurological complications are most common. Nitrous oxide abuse is also associated with psychiatric symptoms, but these have received less attention so far. Vitamin B12 deficiency may play a role in the development of these psychiatric symptoms.

The 1-h fraud detection challenge.

Publications baring falsified and fabricated images appear frequently in the primary literature. Industrialized forms of image forgery as practiced by the so-called paper mills worsen the current situation even further. Good education and awareness within the scientific society are essential to create an environment in which honesty and trust are the prime values in experimental research.

The clinical course and treatment of black mamba ( envenomations: a narrative review.

Context: The black mamba ( is, due to its extremely toxic venom, one of the most dangerous snake species in Sub-Saharan Africa. A bite is a medical emergency and requires adequate action to prevent severe complications. However, there are no comprehensive reviews available based on clinical cases, and no readily accessible guidelines for standardized treatment.

Electrophysiology of hiPSC-Cardiomyocytes Co-Cultured with HEK Cells Expressing the Inward Rectifier Channel.

The immature electrophysiology of human-induced pluripotent stem cell-derived cardiomyocytes (hiCMs) complicates their use for therapeutic and pharmacological purposes. An insufficient inward rectifying current (I) and the presence of a funny current (if) cause spontaneous electrical activity. This study tests the hypothesis that the co-culturing of hiCMs with a human embryonic kidney (HEK) cell-line expressing the Kir2.

Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model.

Introduction: Torsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.

Methods: Dofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions.

The canine chronic atrioventricular block model in cardiovascular preclinical drug research.

Ventricular cardiac arrhythmia is a life threating condition arising from abnormal functioning of many factors in concert. Animal models mirroring human electrophysiology are essential to predict and understand the rare pro- and anti-arrhythmic effects of drugs. This is very well accomplished by the canine chronic atrioventricular block (CAVB) model.

Towards the Development of AgoKirs: New Pharmacological Activators to Study K2.x Channel and Target Cardiac Disease.

Inward rectifier potassium ion channels (I-channels) of the K2.x family are responsible for maintaining a stable negative resting membrane potential in excitable cells, but also play a role in processes of non-excitable tissues, such as bone development. I-channel loss-of-function, either congenital or acquired, has been associated with cardiac disease.

LUF7244 plus Dofetilide Rescues Aberrant K11.1 Trafficking and Produces Functional I.

Voltage-gated potassium 11.1 (K11.1) channels play a critical role in repolarization of cardiomyocytes during the cardiac action potential (AP).