Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives

Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.

Methods

We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).

Results

Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67–0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74–0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70–0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66–0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76–0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74–0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71–0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77–0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74–0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.

Conclusion

Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.     

Power generation using spinel manganese-cobalt oxide as a cathode catalyst for microbial fuel cell applications

This study focused on the use of spinel manganese-cobalt (Mn-Co) oxide, prepared by a solid state reaction, as a cathode catalyst to replace platinum in microbial fuel cells (MFCs) applications. Spinel Mn-Co oxides, with an Mn/Co atomic ratios of 0.5, 1, and 2, were prepared and examined in an air cathode MFCs which was fed with a molasses-laden synthetic wastewater and operated in batch mode. Among the three Mn-Co oxide cathodes and after 300 h of operation, the Mn-Co oxide catalyst with Mn/Co atomic ratio of 2 (MnCo-2) exhibited the highest power generation 113 mW/m2 at cell potential of 279 mV, which were lower than those for the Pt catalyst (148 mW/m2 and 325 mV, respectively). This study indicated that using spinel Mn-Co oxide to replace platinum as a cathodic catalyst enhances power generation, increases contaminant removal, and substantially reduces the cost of MFCs.     

Abdominal dermolipectomy in an abdomen with pre-existing scars: a different concept

Although abdominal dermolipectomy is a frequently performed procedure, few publications have reported on the safety of the procedure in the scarred abdomen. The aim of this study was to stress the possibility of performing a natural-looking abdominoplasty with no complication such as skin necrosis or liponecrosis in the presence of abdominal scars and to clarify that the scarred abdomen is not a great limitation for full abdominoplasty as reported in the literature. Seventy-six abdominoplasties were performed on scarred patients from July of 1997 to June of 2003. Twenty-five patients had oblique subcostal scars, six patients had median supraumbilical scars, three patients had median infraumbilical scars, 10 patients had appendectomy scars, nine patients had paramedian supraumbilical scars, eight patients had paramedian infraumbilical scars, seven patients had long transverse scars of repaired ventral hernias, and eight patients had multiple small scars after laparoscopy. In addition, there were concomitant transverse cesarean delivery scars in 40 patients. All patients underwent full abdominoplasties, plication of the musculoaponeurotic system, and liposuction assistance if required (45 patients). Of 76 subjects, three patients had very limited liponecrosis at the watershed area. Eleven patients (14.5 percent) were morbidly obese and heavy smokers. In comparisons of postabdominoplasty complications, such as liponecrosis, wound infection, and dehiscence with and without liposuction in scarred abdomen, no significant differences were found. Secondary revision was more common among abdominoplasties without liposuction [seven of 45 (15.6 percent) versus 12 of 31 (38.7 percent); p = 0.02]. In conclusion, there is no limitation or contraindication for abdominal dermolipectomy with or without liposuction assistance on the previously scarred abdomen as long as the vascular zones of the abdomen are respected. The abdominal wall dissection is limited to allow only the plication of the musculoaponeurotic system, and aggressive liposuction is avoided.     

Prophylactic effect of aqueous propolis extract against acute experimental hepatotoxicity in vivo

Propolis has been extensively used in folk medicine for the management of a wide spectrum of disorders. In a previous study, we demonstrated the protective effect of the aqueous propolis extract (APE) against the injurious effects of carbon tetrachloride (CCl4) on hepatocytes in vitro. The present investigation was carried out to show whether the hepatoprotective effect of the extract could also be manifested in vivo. Rats were given APE orally for 14 consecutive days, before being subjected to a single intraperitoneal injection of CCl4. One day after the CCl4 injection, the animals were sacrificed, hepatocytes were isolated and liver homogenates were prepared for the assessment of liver injury. In isolated hepatocytes, APE afforded protection against CCl4-induced injury as manifested by a decrease in the leakage of the cytosolic enzyme lactate dehydrogenase (LDH), decreased generation of lipid peroxide and maintenance of cellular reduced glutathione (GSH) content. In principle, similar findings were observed in liver homogenates. The present findings show that APE has in vivo hepatoprotective potential which could be attributed at least in part to the maintenance of cellular GSH content. The latter effect seems to play an important role in conserving the integrity of biomembranes as it was associated with a decrease in lipid peroxidation and reduced leakage of cytosolic LDH.     

Effect of vitamins and cell constructions on the activity of microbial fuel cell battery

Construction of efficient performance of microbial fuel cells (MFCs) requires certain practical considerations. In the single chamber microbial fuel cell, there is no border between the anode and the cathode, thus the diffusion of the dissolved oxygen has a contrary effect on the anodic respiration and this leads to the inhibition of the direct electron transfer from the biofilm to the anodic surface. Here, a fed-batch single chambered microbial fuel cells are constructed with different distances 3 and 6?cm (anode- cathode spacing), while keeping the working volume is constant. The performance of each MFC is individually evaluated under the effects of vitamins & minerals with acetate as a fed load. The maximum open circuit potential during testing the 3 and 6?cm microbial fuel cells is about 946 and 791?mV respectively. By decreasing the distance between the anode and the cathode from 6 to 3?cm, the power density is decreased from 108.3?mW?m^?2 to 24.5?mW?m^?2. Thus, the short distance in membrane-less MFC weakened the cathode and inhibited the anodic respiration which affects the overall performance of the MFC efficiency. The system is displayed a maximum potential of 564 and 791?mV in absence & presence of vitamins respectively. Eventually, the overall functions of the acetate single chamber microbial fuel cell can be improved by the addition of vitamins & minerals and increasing the distance between the cathode and the anode.     

Characterization of transgenic poplar with ectopic expression of pine cytosolic glutamine synthetase under conditions of varying nitrogen availability

The present study addresses the hypothesis that enhanced expression of glutamine synthetase (GS) in transgenic poplar, characterized by the ectopic expression of pine cytosolic GS, results in an enhanced efficiency of nitrogen (N) assimilation and enhanced growth. Transgenic and control poplar were supplied with low and high N levels and the role of ectopic expression of the pine GS in growth and N assimilation was assessed by using amino acid analysis, (15)N enrichment, biochemical analyses, and growth measurements. While leaves of transgenic poplar contained 85% less (P < 0.01) free ammonium than leaves of nontransgenic control plants, leaves of transgenics showed increases in the levels of free glutamine and total free amino acids. Transgenic poplar lines also displayed significant increases in growth parameters when compared with controls grown under both low (0.3 mm) and high (10 mm) nitrate conditions. Furthermore, (15)N-enrichment experiments showed that 27% more (P < 0.05) (15)N was incorporated into structural compounds in transgenic lines than in nontransgenic controls. Using the methods described here, we present direct evidence for increased N assimilation efficiency and growth in GS transgenic lines.     

Does allelopathy involve in the association pattern of Trifolium resupinatum?

Indoor experiments demonstrated that allelopathic potential of rosette and flowering plants of qort is an important factor explaining the growth reduction of its associated species. Aqueous tissue extracts of flowering plants exhibited strong inhibitory effects on the germination percentage and radicle growth rate of the tested species as compared with those of vegetative plants. Under laboratory conditions, this inhibition was in agreement with toxicity assessments of soil samples collected from the rhizosphere of T. resupinatum L., where shoot and root dry mass of the tested species were significantly reduced. Detoxification of allelochemicals by presence of activated carbon can eliminate the inhibitory effects of the different extracts. This technique clarifies the occurrence of allelopathic interference by qort on seed germination and seedling growth, and hence suspects the allelopathic potential of qort in the growth reduction of associate species under field conditions along with competition. This revised version was published online in August 2006 with corrections to the Cover Date.     

Applying Ligands Profiling Using Multiple Extended Electron Distribution Based Field Templates and Feature Trees Similarity Searching in the Discovery of New Generation of Urea-Based Antineoplastic Kinase Inhibitors

This study provides a comprehensive computational procedure for the discovery of novel urea-based antineoplastic kinase inhibitors while focusing on diversification of both chemotype and selectivity pattern. It presents a systematic structural analysis of the different binding motifs of urea-based kinase inhibitors and the corresponding configurations of the kinase enzymes. The computational model depends on simultaneous application of two protocols. The first protocol applies multiple consecutive validated virtual screening filters including SMARTS, support vector-machine model (ROC = 0.98), Bayesian model (ROC = 0.86) and structure-based pharmacophore filters based on urea-based kinase inhibitors complexes retrieved from literature. This is followed by hits profiling against different extended electron distribution (XED) based field templates representing different kinase targets. The second protocol enables cancericidal activity verification by using the algorithm of feature trees (Ftrees) similarity searching against NCI database. Being a proof-of-concept study, this combined procedure was experimentally validated by its utilization in developing a novel series of urea-based derivatives of strong anticancer activity. This new series is based on 3-benzylbenzo[d]thiazol-2(3H)-one scaffold which has interesting chemical feasibility and wide diversification capability. Antineoplastic activity of this series was assayed in vitro against NCI 60 tumor-cell lines showing very strong inhibition of GI₅₀ as low as 0.9 uM. Additionally, its mechanism was unleashed using KINEX™ protein kinase microarray-based small molecule inhibitor profiling platform and cell cycle analysis showing a peculiar selectivity pattern against Zap70, c-src, Mink1, csk and MeKK2 kinases. Interestingly, it showed activity on syk kinase confirming the recent studies finding of the high activity of diphenyl urea containing compounds against this kinase. Allover, the new series, which is based on a new kinase scaffold with interesting chemical diversification capabilities, showed that it exhibits its “emergent” properties by perturbing multiple unexplored kinase pathways.