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Additional file 1. Additional tables and figures.

Additional file 1. Supplementary tables (Tables S1–S3) comprehensively summarizing in-depth information of findings from the key studies included in the review.

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 mitochondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arrhythmia 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 mitochondrial 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 production. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of cardiac mitochondrial dysfunction caused by severe oxidative stress.

This paper reviews the reported pharmacological properties of protocatechuic acid (PCA, 3,4-dihydroxy benzoic acid), a type of phenolic acid found in many food plants such as olives and white grapes. PCA is a major metabolite of anthocyanin. The pharmacological actions of PCA have been shown to include strong in vitro and in vivo antioxidant activity. In in vivo experiments using rats and mice, PCA has been shown to exert anti-inflammatory as well as antihyperglycemic and antiapoptotic activities. Furthermore, PCA has been shown to inhibit chemical carcinogenesis and exert proapoptotic and antiproliferative effects in different cancerous tissues. Moreover, in vitro studies have shown PCA to have antimicrobial activities and also to exert synergistic interaction with some antibiotics against resistant pathogens. This review aims to comprehensively summarize the pharmacological properties of PCA reported to date with an emphasis on its biological properties and mechanisms of action which could be therapeutically useful in a clinical setting.

BACKGROUND: A higher prevalence of QT prolongation has been reported among human immunodeficiency virus (HIV)‐infected patients. Previous studies have demonstrated that QT dispersion is a better predictor of serious ventricular tachyarrhythmia and cardiac mortality than corrected QT (QTc) interval. However, data of QT dispersion in HIV‐infected patients receiving a combined antiretroviral therapy (cART) is limited. We sought to assess QTc interval and QT dispersion in HIV‐infected patients receiving cART. The association between QT parameters and heart rate variability (HRV) was also examined. METHODS: Ninety‐one HIV‐infected patients receiving cART (male = 33, mean age = 44 ± 10 years) and 70 HIV‐seronegative subjects (male = 25, mean age = 44 ± 8 years) were enrolled in the study. In a resting 12‐lead electrocardiogram, QT interval was measured by the tangent method in all leads with well‐defined T waves. The QT dispersion was defined as the difference between maximum and minimum QTc intervals in any of 12 leads. RESULTS: The baseline characteristics were not different between the two groups. We demonstrated the significantly longer mean QTc interval (420 ± 21 vs. 409 ± 21 ms, P < 0.001), and greater QT dispersion in HIV‐infected group compared to the control group (85 ± 29 vs. 55 ± 23 ms, P < 0.001). Among the HIV‐infected patients, those who had lower CD4 lymphocyte count (

Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance.Male Wistar rats weighing 180-200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg(-1)·day(-1)), sitagliptin (30 mg·kg(-1)·day(-1)) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined.Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV.Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats.

BACKGROUND: Previous studies have demonstrated the presence of autonomic dysfunction in human immunodeficiency virus (HIV)‐infected patients. However, the data in those receiving combination antiretroviral therapy (cART) are conflicting. The aim of this study was to assess the autonomic function using heart rate variability (HRV) and heart rate turbulence (HRT) analysis in HIV‐infected patients receiving cART. METHODS: Eighty‐one HIV‐infected patients receiving cART and 42 control subjects were enrolled in the study. The HRV and HRT parameters were assessed on 24‐hour digital Holter electrocardiogram recordings. RESULTS: Baseline characteristics were comparable between HIV‐infected and control subjects, except the higher fasting glucose and triglyceride and lower high‐density lipoprotein cholesterol observed in HIV‐infected patients. All components of HRV were significantly reduced in HIV‐infected patients. After adjustment with biochemical parameters, most of the HRV parameters were still significantly reduced in HIV‐infected patients. However, HRV parameters reflecting vagal activity were no longer different between 2 groups. In addition, HRT parameters did not differ between HIV‐infected and control subjects. The standard deviation of normal‐to‐normal intervals significantly correlated with CD4 lymphocyte counts in HIV‐infected patients but did not with protease inhibitors therapy. CONCLUSIONS: We demonstrated the overall decrease in HRV in HIV‐infected patients receiving cART. The metabolic disturbance observed in HIV‐infected patients possibly accounted for decreased vagal activity.