Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a

This study was designed to investigate the hemodynamic effect of rolipram, a phosphodiesterase type 4 (PDE4) inhibitor, in normal rat hearts both in vivo and in vitro and its underlying mechanism. The pressure-volume loop, isolated heart, and Ca2+ transients triggered by field stimulation or caffeine were used to analyze the hemodynamic mechanism of rolipram. The results demonstrated that rolipram (3 mg/kg, ip) significantly increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-systolic volume, end-diastolic volume, end-systolic pressure, heart rate, ejection fraction, peak rate of rise of left pressure (+dp/dtmax), the slopes of end-systolic pressure-volume relationship (slope of ESPVR) named as left ventricular end-systolic elastance, and reduced the slopes of end-diastolic pressure-volume relationship (slope of EDPVR). Meanwhile, the systolic blood pressure, diastolic blood pressure, and pulse pressure were significantly enhanced by rolipram. Also, rolipram deviated normal ventricular-arterial coupling without changing the arterial elastance. Furthermore, rolipram (0.1, 1, 10 μM) also exerted positive inotropic effect in isolated rat hearts by increasing the left ventricular development pressure, and +dp/dtmax in non-paced and paced modes. Rolipram (10 μM) increased the SERCA2a activity, Ca2+ content, and Ca2+ leak rate without changing diastolic Ca2+ level. Rolipram had significant positive inotropic effect with less effect on peripheral vascular elastance and its underlying mechanism was mediated by increasing SERCA2a activity. PDE4 inhibition by rolipram resulted in a positive inotropic effect and might serve as a target for developing agents for the treatment of heart failure in clinical settings

Evaluation of Platelet Distribution Width as an Early Predictor of Acute Kidney Injury in Extensive Burn Patients

Background. The extensive burns devastate trauma. The research was designed to analyse the predictive value of early platelet (PLT) indices on the development of acute kidney injury (AKI) after severe burns. Methods and Results. 186 patients with extensive burns (burn area ≥30%) were eventually involved. Multivariate analyses pointed out that platelet distribution width (PDW) in the first 24 h after admission was an independent risk factor for AKI, severe AKI, and RRT requirement in patients with severe burns, and AKI risk showed an increase of 30.9% per increase of 1% in PDW (OR = 1.309, CI, 1.075–1.594, and P = 0.007). It was found that the area under the ROC curve (AUC) of PDW predicting AKI was 0.735 and that the AUC value was 0.81 for AKI after combining PDW and blood urea nitrogen (BUN). Based on the cut-off value PDW = 17.7%, patients were divided into high- (PDW ≥17.7%) and low-risk (PDW 17.7%, burn patients are not only at a higher risk for AKI but may also have higher AKI severity. Due to low cost and wide availability, PDW has the potential to be the tool that can predict AKI in extensive burn patients

Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a

This study was designed to investigate the hemodynamic effect of rolipram, a phosphodiesterase type 4 (PDE4) inhibitor, in normal rat hearts both in vivo and in vitro and its underlying mechanism. The pressure-volume loop, isolated heart, and Ca2+ transients triggered by field stimulation or caffeine were used to analyze the hemodynamic mechanism of rolipram. The results demonstrated that rolipram (3 mg/kg, ip) significantly increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-systolic volume, end-diastolic volume, end-systolic pressure, heart rate, ejection fraction, peak rate of rise of left pressure (+dp/dt(max)), the slopes of end-systolic pressure-volume relationship (slope of ESPVR) named as left ventricular end-systolic elastance, and reduced the slopes of end-diastolic pressure-volume relationship (slope of EDPVR). Meanwhile, the systolic blood pressure, diastolic blood pressure, and pulse pressure were significantly enhanced by rolipram. Also, rolipram deviated normal ventricular-arterial coupling without changing the arterial elastance. Furthermore, rolipram (0.1, 1, 10 mu M) also exerted positive inotropic effect in isolated rat hearts by increasing the left ventricular development pressure, and +dp/dt(max) in non-paced and paced modes. Rolipram (10 mu M) increased the SERCA2a activity, Ca(2+ )content, and Ca(2+ )leak rate without changing diastolic Ca2+ level. Rolipram had significant positive inotropic effect with less effect on peripheral vascular elastance and its underlying mechanism was mediated by increasing SERCA2a activity. PDE4 inhibition by rolipram resulted in a positive inotropic effect and might serve as a target for developing agents for the treatment of heart failure in clinical settings

Composition, function and succession of bacterial communities in the tomato rhizosphere during continuous cropping

The bacteria that dominate and become enriched in the rhizosphere during continuous cropping are of increasing interest, as they can greatly adapt to the rhizosphere. However, there are still little knowledge about the general composition and function of these bacteria. In this study, we planted tomatoes in three different soils for three planting cycles and used both high-throughput sequencing and culture-dependent workflows. Despite significant differences in bacterial communities from the initial soils, we observed a similar succession in the rhizosphere bacterial community compositions. We identified certain bacteria that were gradually enriched and potentially beneficial, such as Rhizobium and Flavobacterium. However, some other potentially beneficial bacteria, such as Massilia and Lysobacter, were gradually depleted. Additionally, we found that predicted functions related to xenobiotic biodegradation, nutrient metabolism and antibiotic biosynthesis were enriched in different rhizosphere soils. Beijerinckia fluminensis GR2, which was gradually enriched in all tested soils, significantly inhibited the growth of Ralstonia solanacearum and protected the host from infection. Our study provides new insights into the assembly mechanism of gradually enriched bacteria and their role as plant-beneficial microbes that adapt well to the rhizosphere