Phosphodiesterase-3 inhibitor （cilostazol） attenuates oxidative stress-induced mitochondrial dysfunction in the heart

Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.     

Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold

INTRODUCTION: Ventricular defibrillation is probabilistic and shock strength dependent. We investigated the relationship between defibrillation outcome and postshock activation patterns for shocks of the same strength (approximately 50% probability of success for defibrillation [ED50] to yield an equal number of successful and failed shocks). METHODS AND RESULTS: In five pigs, 10 shocks of approximately ED50 strength (right ventricle-superior vena cava, biphasic, 6/4 msec) were delivered after 10 seconds of ventricular fibrillation (VF). Epicardial activation sequences following shocks were mapped with a 504-electrode shock and analyzed by animating dV/dt of the electrograms. Intercycle interval (ICI, time between the onset of successive postshock cycles), wavefront conduction time (WCT, time between the earliest and latest activation of a cycle), and overlapping index (WCT of cycle[n]/ICI of cycle[n+1]) were determined for the first five postshock cycles. An overlapping index >1 indicates overlap between successive cycles. Of 50 defibrillation attempts, 25 were successes. There was no difference between successful and failed episodes for both ICI (68 +/- 9 msec vs 62 +/- 10 msec) and WCT (97 +/- 24 msec vs 100 +/- 14 msec) of cycle 1. However, starting at cycle 2, the ICI was longer, and the WCT was shorter for successful than failed episodes (P < 0.01). Overlapping cycles (index > 1) were found during the transition from cycles 2 through 5 in all failed (index >1) and in no successful episodes. CONCLUSIONS: (1) Defibrillation outcome cannot be determined during the first postshock cycle. (2) At least three rapid successive cycles with overlap of cycles 2 and 3 are present in all failed and in no successful episodes. (3) The overlapping index is a marker to predict defibrillation outcome.     

Cardiac mortality is associated with low levels of omega-3 and omega-6 fatty acids in the heart of cadavers with a history of coronary heart disease

The benefits of omega-3 (ie, eicosapentaenoic acid and docosahexaenoic acid [DHA]) and omega-6 (ie, linoleic acid and arachidonic acid [AA]) fatty acids on reducing cardiac mortality are still debated. In this study, we tested the hypothesis that high levels of omega-3 and omega-6 fatty acids in heart tissues are associated with low cardiac mortality in Thai cadavers. One hundred fresh cadavers were examined in this study. The cause of death, history of coronary heart disease (CHD), and fish consumption habits were obtained from death certificates, cadaver medical record profiles, and a questionnaire to a person who lived with the subject before death. In each cadaver, biopsies of cardiac tissues were taken from the interventricular septum for measurement of fatty acid. Of the 100 cadavers (average age, 69 ± 13 years), 60 were men. The frequency of fish consumption was directly associated with omega-3 and omega-6 fatty acids in heart tissues (P < .01). History of CHD and cause of death (cardiac vs noncardiac) were not significantly associated with levels of omega-3 or omega-6 fatty acids. However, in cadavers with a history of CHD, high levels of omega-3 and omega-6, particularly DHA and AA, were associated with low cardiac mortality (P < .05). Fish consumption is associated with levels of omega-3 and omega-6 fatty acids in heart tissues. Although omega-3 and omega-6 fatty acids are not associated with cardiac mortality in the overall studied population, their low levels (especially DHA and AA) in heart tissues are associated with high cardiac mortality in cadavers with a history of CHD.     

Bone Age Assessment in Young Children Using Automatic Carpal Bone Feature Extraction and Support Vector Regression

Boundary extraction of carpal bone images is a critical operation of the automatic bone age assessment system, since the contrast between the bony structure and soft tissue are very poor. In this paper, we present an edge following technique for boundary extraction in carpal bone images and apply it to assess bone age in young children. Our proposed technique can detect the boundaries of carpal bones in X-ray images by using the information from the vector image model and the edge map. Feature analysis of the carpal bones can reveal the important information for bone age assessment. Five features for bone age assessment are calculated from the boundary extraction result of each carpal bone. All features are taken as input into the support vector regression (SVR) that assesses the bone age. We compare the SVR with the neural network regression (NNR). We use 180 images of carpal bone from a digital hand atlas to assess the bone age of young children from 0 to 6 years old. Leave-one-out cross validation is used for testing the efficiency of the techniques. The opinions of the skilled radiologists provided in the atlas are used as the ground truth in bone age assessment. The SVR is able to provide more accurate bone age assessment results than the NNR. The experimental results from SVR are very close to the bone age assessment by skilled radiologists.     

Triple synchronous primary cervical,endometrial and ovarian cancer with four different histologic patterns

Background Double synchronous primary cancers of gynecological cancers is a common event. However, triple synchronous primary gynecological cancers is an extremely rare event. Case A 50-year-old woman, para 0-0-0-0 was admitted to the hospital with a complaint of menorrhagia for 2 months. The preoperative evaluation and diagnosis was myoma uteri with bilateral ovarian tumor. Subtotal hysterectomy with bilateral salpingo-oophorectomy, and omentectomy were performed. The postoperative and pathologic findings were adenosquamous carcinoma of the endocervix, adenocarcinoma of the endometrium, low malignant potential of the right ovary and mucinous cystadenocarcinoma of the left ovary. She received a complete course of whole pelvic radiation. Unfortunately, she died from pulmonary embolism. Conclusion The occurrence of triple synchronous gynecological cancers is a rare and unique event deserving further studies