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Background: Magnolol, a compound isolated from the cortex of Magnolia officinalis, has been found to possess anti-allergic and anti-asthmatic activity. Methods: The effect of magnolol on ionic currents was studied in cultured smooth muscle cells of human trachea with the aid of the patch clamp technique. Results: In whole cell current recordings mognolol reversibly increased the amplitude of K2+ outward currents. The increase in outward current caused by magnolol was sensitive to inhibition by iberiotoxin (200 nM) or paxilline (1 μM) but not by glibenclamide (10 μM). In inside out patches, magnolol added to the bath did not modify single channel conductance but effectively enhanced the activity of large conductance Ca2+ activated K+ (BKCa) channels. Magnolol increased the probability of these channel openings in a concentration dependent manner with an EC50 value of 1 .5 μM. The magnolol stimulated increase in the probability of channels opening was independent of internal Ca2+. The application of magnolol also shifted the activation curve of BKCa channels to less positive membrane potentials. The change in the kinetic behaviour of BKCa channels caused by magnolol in these cells is the result of an increase in dissociation and gating constants. Conclusions: These results provide evidence that, in addition to the presence of antioxidative activity, magnolol is potent in stimulating BKCa channel activity in tracheal smooth muscle cells. The direct stimulation of these BKCa channels by magnolol may contribute to the underlying mechanism by which it acts as an anti-asthmatic compound. [ABSTRACT FROM AUTHOR]

Objective: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population., Methods: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing., Results: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features., Conclusion: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists., Competing Interests: All authors have disclosed no conflicts of interest.

OBJECTIVE. To report the initial experience in using cryoballoon catheter ablation in the treatment of atrial fibrillation in Hong Kong. DESIGN. Single-centre, prospective case series. SETTING. Regional hospital, Hong Kong. PATIENTS. Sixteen patients (mean age, 55 years; standard deviation, 14 years; 11 males) with paroxysmal (n=12) or persistent (n=4) atrial fibrillation. INTERVENTIONS. Pulmonary vein isolation by ablation with a 28-mm cryoballoon catheter. MAIN OUTCOME MEASURES. Safety, effectiveness, and learning curve of this procedure. RESULTS. Of 67 pulmonary veins, 61 (91%) could be successfully isolated with the cryoballoon alone. The remaining pulmonary veins were isolated with additional ablation using an 8-mm tip cryocatheter. One phrenic nerve palsy developed during right middle pulmonary vein ablation, which resolved. Another patient endured a minor guidewire dissection of the right inferior pulmonary vein. The mean (standard deviation) procedural and fluoroscopic times were 231 (32) and 62 (18) minutes, respectively. On comparing the first nine and last seven procedures, there was a significant improvement in procedural time (mean [standard deviation], 244 [32] vs 213 [24] minutes; P=0.04) and in the fluoroscopic time (70 [21] vs 51 [7] minutes; P=0.038). With a median follow-up of 21 months, nine (75%) of the 12 patients with paroxysmal atrial fibrillation and one (25%) of those four with persistent atrial fibrillation had no recurrence, without the use of anti-arrhythmic drugs. CONCLUSIONS. Pulmonary vein isolation by cryoballoon catheter ablation is safe and effective in treating patients with paroxysmal, but not for patients with persistent atrial fibrillation. A relatively short learning curve of around 10 cases was deemed appropriate.

The effects of ceramide on ion currents in rat pituitary GH(3) cells were investigated. Hyperpolarization-elicited K(+) currents present in GH(3) cells were studied to determine the effect of ceramide and other related compounds on the inwardly rectifying K(+) current (I(K(IR))). Ceramide (C(2)-ceramide) suppressed the amplitude of I(K(IR)) in a concentration-dependent manner, with an IC(50) value of 5 microM. Ceramide caused a rightward shift in the midpoint for the activation curve of I(K(IR)). Pretreatment with PD-98059 (30 microM) or U-0126 (30 microM) did not prevent ceramide-mediated inhibition of I(K(IR)). However, the magnitude of ceramide-induced inhibition of I(K(IR)) was attenuated in GH(3) cells preincubated with dithiothreitol (10 microM). TNF alpha (100 ng/g) also suppressed I(K(IR)). In the inside-out configuration, application of ceramide (30 microM) to the bath slightly suppressed the activity of large conductance Ca(2+)-activated K(+) channels. Under the current clamp mode, ceramide (10 microM) increased the firing of action potentials. Cells that exhibited an irregular firing pattern were converted to those displaying a regular firing pattern after application of ceramide (10 microM). Ceramide also suppressed I(K(IR)) in neuroblastoma IMR-32 cells. Therefore, ceramide can produce a depressant effect on I(K(IR)). The blockade of this current by ceramide may affect cell function.