Intra-prefrontal cyclosporine potentiates ketamine-induced fear extinction in rats.

Several brain regions, including the medial prefrontal cortex (mPFC), are important in the process of fear extinction learning. Ketamine is a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, which is shown to play a role in extinction modulation. Ketamine and calcineurin (CN), an intracellular protein phosphatase, have several common targets in the cells. Therefore, in the present study, our aim is to investigate the possible role of calcineurin in the mPFC on the enhancing effects of ketamine in fear extinction. First, different doses of a CN inhibitor, cyclosporine-A (CsA), were micro-injected into the infralimbic (IL) region of the mPFC prior to extinction training in a classical conditioning model in rats. Next, sub-effective doses of CsA (Intra-mPFC) and ketamine (i.p.) were co-administered in another cohort of rats to find their possible interactions. Enzymatic activity of calcineurin was measured in the IL-mPFC following drug administration. We used the elevated plus-maze (EPM) and open field (OF) test for further behavioral assessments. The results showed that CsA can enhance the extinction of conditioned fear and inhibit the enzyme CN at a dose of 20 nM. The combination of sub-effective doses of CsA (5 nM) and ketamine (10 mg/kg) could again enhance the extinction of fear and reduce CN activity in the region. Our results propose that inhibition of CN in the IL-mPFC is involved in the extinction of fear and ketamine enhancement of extinction is probably mediated by reducing CN activity in this part of the brain.

Analysis of QTc Interval during Levofloxacin Prescription in Cardiac Patients with Pneumonia.

BACKGROUND: Medications induced QT prolongation could cause ventricular arrhythmia, torsade de pointes, and death. OBJECTIVE: The purpose of this study was to evaluate the magnitude of QTc interval prolongation as a result of levofloxacin treatment in patients admitted to cardiology wards. METHODS: This was a cross-sectional study conducted in the coronary care units and general wards of the Imam Ali Heart Hospital in Kermanshah, Iran. The QTc interval was determined at baseline and after 72 hours of levofloxacin administration. Changes in the QTc interval before and after the levofloxacin prescription were determined. RESULTS: The mean age of recruited patients was 63.26 ± 14.56 years. More than 80% of patients who received levofloxacin experienced QTc prolongation. The QTc interval was increased significantly after levofloxacin administration (15.68 ± 26.84 milliseconds) (p<0.001). These changes remained significant after excluding medications with QTc lengthening properties (p<0.001). CONCLUSION: Treatment with levofloxacin in patients with heart disease increases the risk of QT prolongation.