High-Dose Acetaminophen with -acetylcysteine Rescue Inhibits M2 Polarization of Tumor-Associated Macrophages.

High-dose acetaminophen (AAP) with -acetylcysteine (NAC) rescue is among the few treatments that has shown activity in phase I trials without achieving dose-limiting toxicity that has not progressed to evaluation in later line studies. While the anti-tumor effects of AAP/NAC appear not to be mediated by glutathione depletion and free radical injury, the mechanism of anti-tumor effects of AAP/NAC has not been definitively characterized. In vitro, the effects of AAP/NAC were evaluated on bone marrow derived macrophages.

Post-extrasystolic potentiation as a predictor of premature ventricular contraction-cardiomyopathy in an animal model.

Aims: High premature ventricular contractions (PVCs) burden does not always predict the development of PVC-cardiomyopathy (CM). We sought to evaluate post-extrasystolic potentiation (PESP) of left ventricular ejection fraction (LVEF) to predict the severity of PVC-CM in an animal model.

Methods And Results: Right ventricular apical bigeminal PVCs were introduced for 12 weeks in 11 canines to induce PVC-CM.

Persistent Proarrhythmic Neural Remodeling Despite Recovery From Premature Ventricular Contraction-Induced Cardiomyopathy.

Background: The presence and significance of neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown.

Objectives: This study aimed to characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM.

Methods: In 12 canines, the investigators implanted epicardial pacemakers and radiotelemetry units to record cardiac rhythm and nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus (VNA), and arterial blood pressure.

Compromised axon initial segment integrity in EAE is preceded by microglial reactivity and contact.

Axonal pathology is a key contributor to long-term disability in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), but the mechanisms that underlie axonal pathology in MS remain elusive. Evidence suggests that axonal pathology is a direct consequence of demyelination, as we and others have shown that the node of Ranvier disassembles following loss of myelin. In contrast to the node of Ranvier, we now show that the axon initial segment (AIS), the axonal domain responsible for action potential initiation, remains intact following cuprizone-induced cortical demyelination.