Comparing the Clinical Outcomes between Drug Eluting Stents and Bare Metal Stents in Patients with Insulin-Treated Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials

BackgroundSeveral studies have shown Drug Eluting Stents (DES) to be better compared to Bare Metal Stents (BMS) in patients with type 2 Diabetes Mellitus (T2DM). Since, the adverse clinical outcomes in patients with Insulin-Treated Type 2 Diabetes Mellitus (ITDM) implanted with DES and BMS have not been previously studied, we aim to compare the clinical outcomes in similar patients with cardiovascular diseases, treated with DES and BMS.MethodsRandomized Controlled Trials (RCTs) comparing patients treated with DES and BMS were searched from PubMed and EMBASE databases. Outcome data for the patients with ITDM were carefully extracted. Major Adverse Cardiac Events (MACEs), mortality, Target Vessel Revascularization (TVR), Target Lesion Revascularization (TLR), Myocardial Infarction (MI) and Stent Thrombosis (ST) were considered as the clinical endpoints for this analysis. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated and the pooled analyses were performed with RevMan 5.3 software.ResultsTen RCTs consisting of 830 patients with ITDM (477 patients in the DES group and 353 patients in the BMS group) from a total number of 9,141 patients were included in this analysis. During a follow-up period from one month to one year, MACEs were not increased with the use of DES in these patients with ITDM. At 9 months, MACEs were significantly lower in the DES group with OR: 0.40, 95% CI: 0.23–0.72; P = 0.002 with no increase in mortality. TVR and TLR also favored the DES group with OR: 0.44, 95% CI: 0.22–0.88, P = 0.02 and OR: 0.28, 95% CI: 0.14–0.53; P = 0.0001 respectively at 9 months, and OR: 0.46, 95% CI: 0.23–0.94, P = 0.03 and OR: 0.28, 95% CI: 0.14–0.55; P = 0.0003 respectively at one year. Results for MI, and ST were not statistically significant.ConclusionCompared to BMS, DES were associated with a significantly lower rate of repeated revascularization, without any increase in MACEs or mortality in these patients with ITDM during a follow up period of one year. However, due to the very small population size, further studies with a larger number of randomized patients are required to completely solve this issue.     

Glutathione reductase (EC 1.6.4.2.) in experimental trypanosomiasis

The activity of glutathione reductase (GHSR) in extracts of kidney, liver and testis of rats infected with Trypanosoma congolense decreased with every wave of parasitemia. The implications of these observations as they relate to the risk of oxidative stress are discussed.     

Lack of correlation between fibrinolysis and the transformed state of cultured mammalian cells

Transformed cells in culture have been reported by others to exhibit high levels of extracellular proteolytic (fibrinolytic) activity due to plasminogen activation, compared to low levels from nontransformed cells. Enhanced fibrinolysis was accordingly proposed to be a reliable and general enzymatic change associated with cell transformation.In the present study, ten different types of serially cultured, growing cells were examined for their extracellular fibrinolytic activity. The level of the fibrinolytic activity was found not to correlate with the transformed or nontransformed state of these cells.     

Melittin peptides exhibit different activity on different cells and model membranes

Melittin (MLT) is a lytic peptide with a broad spectrum of activity against both eukaryotic and prokaryotic cells. To understand the role of proline and the thiol group of cysteine in the cytolytic activity of MLT, native MLT and cysteine-containing analogs were prepared using solid phase peptide synthesis. The antimicrobial and cytolytic activities of the monomeric and dimeric MLT peptides against different cells and model membranes were investigated. The results indicated that the proline residue was necessary for antimicrobial activity and cytotoxicity and its absence significantly reduced lysis of model membranes and hemolysis. Although lytic activity against model membranes decreased for the MLT dimer, hemolytic activity was increased. The native peptide and the MLT-P14C monomer were mainly unstructured in buffer while the dimer adopted a helical conformation. In the presence of neutral and negatively charged vesicles, the helical content of the three peptides was significantly increased. The lytic activity, therefore, is not correlated to the secondary structure of the peptides and, more particularly, on the propensity to adopt helical conformation.     

Membrane interactions and biological activity of antimicrobial peptides from Australian scorpion

UyCT peptides are antimicrobial peptides isolated from the venom of the Australian scorpion. The activity of the UyCT peptides against Gram positive and Gram negative bacteria and red blood cells was determined. The membrane interactions of these peptides were evaluated by dye release (DR) of the fluorophore calcein from liposomes and isothermal titration calorimetry (ITC); and their secondary structure was determined by circular dichroism (CD). Three different lipid systems were used to mimic red blood cells, Escherichia coli and Staphylococcus aureus membranes. UyCT peptides exhibited broad spectrum antimicrobial activity with low MIC for S. aureus and multi-drug resistant Gram negative strains. Peptide combinations showed some synergy enhancing their potency but not hemolytic activity. The UyCT peptides adopted a helical structure in lipid environments and DR results confirmed that the mechanism of action is by disrupting the membrane. ITC data indicated that UyCT peptides preferred prokaryotic rather than eukaryotic membranes. The overall results suggest that UyCT peptides could be pharmaceutical leads for the treatment of Gram negative multiresistant bacterial infections, especially against Acinetobacter baumanni, and candidates for peptidomimetics to enhance their potency and minimize hemolysis. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.     

Italian natural history museums on the verge of collapse?

The Italian natural history museums are facing a critical situation, due to the progressive loss of scientific relevance, decreasing economic investments, and scarcity of personnel. This is extremely alarming, especially for ensuring the long-term preservation of the precious collections they host. Moreover, a commitment in fieldwork to increase scientific collections and concurrent taxonomic research are rarely considered priorities, while most of the activities are addressed to public events with political payoffs, such as exhibits, didactic meetings, expositions, and talks. This is possibly due to the absence of a national museum that would have better steered research activities and overall concepts for collection management. We here propose that Italian natural history museums collaborate to instate a “metamuseum”, by establishing a reciprocal interaction network aimed at sharing budgetary and technical resources, which would assure better coordination of common long-term goals and scientific activities.     

Isolation and characterization of cellulose-degrading bacteria from the deep subsurface of the Homestake gold mine,Lead, South Dakota,USA

The present study investigated the cultivable mesophilic (37°C) and thermophilic (60°C) cellulose-degrading bacterial diversity in a weathered soil-like sample collected from the deep subsurface (1.5 km depth) of the Homestake gold mine in Lead, South Dakota, USA. Chemical characterization of the sample by X-ray fluorescence spectroscopy revealed a high amount of toxic heavy metals such as Cu, Cr, Pb, Ni, and Zn. Molecular community structures were determined by phylogenetic analysis of 16S rRNA gene sequences retrieved from enrichment cultures growing in presence of microcrystalline cellulose as the sole source of carbon. All phylotypes retrieved from enrichment cultures were affiliated to Firmicutes. Cellulose-degrading mesophilic and thermophilic pure cultures belonging to the genera Brevibacillus, Paenibacillus, Bacillus, and Geobacillus were isolated from enrichment cultures, and selected cultures were studied for enzyme activities. For a mesophilic isolate (DUSELG12), the optimum pH and temperature for carboxymethyl cellulase (CMCase) were 5.5 and 55°C, while for a thermophilic isolate (DUSELR7) they were 5.0 and 75°C, respectively. Furthermore, DUSELG12 retained about 40% CMCase activity after incubation at 60°C for 8 h. Most remarkably, thermophilic isolate, DUSELR7 retained 26% CMCase activity at 60°C up to a period of 300 h. Overall, the present work revealed the presence of different cellulose-degrading bacterial lineages in the unique deep subsurface environment of the mine. The results also have strong implications for biological conversion of cellulosic agricultural and forestry wastes to commodity chemicals including sugars.     

Microbial and Mineralogical Characterizations of Soils Collected from the Deep Biosphere of the Former Homestake Gold Mine, South Dakota

A microbial census on deep biosphere (1.34 km depth) microbial communities was performed in two soil samples collected from the Ross and number 6 Winze sites of the former Homestake gold mine, Lead, South Dakota using high-density 16S microarrays (PhyloChip). Soil mineralogical characterization was carried out using X-ray diffraction, X-ray photoelectron, and Mössbauer spectroscopic techniques which demonstrated silicates and iron minerals (phyllosilicates and clays) in both samples. Microarray data revealed extensive bacterial diversity in soils and detected the largest number of taxa in Proteobacteria phylum followed by Firmicutes and Actinobacteria. The archael communities in the deep gold mine environments were less diverse and belonged to phyla Euryarchaeota and Crenarchaeota. Both the samples showed remarkable similarities in microbial communities (1,360 common OTUs) despite distinct geochemical characteristics. Fifty-seven phylotypes could not be classified even at phylum level representing a hitherto unidentified diversity in deep biosphere. PhyloChip data also suggested considerable metabolic diversity by capturing several physiological groups such as sulfur-oxidizer, ammonia-oxidizers, iron-oxidizers, methane-oxidizers, and sulfate-reducers in both samples. High-density microarrays revealed the greatest prokaryotic diversity ever reported from deep subsurface habitat of gold mines.     

Synthesis and secondary structure in membranes of the Bcl-2 anti-apoptotic domain BH4.

Solid phase synthesis of BH4, the 26 amino-acid domain (6RTGYDNREIVMKYIHYKLSQRGYEWD31) of the anti-apoptotic Bcl-2 protein has been accomplished using Fmoc chemistry. The use of peculiar cleavage conditions provided high yields after purification such that tens to hundreds of mg could be obtained. A 15N-labelled version of the peptide could also be synthesized for NMR studies in membranes. The peptide purity was not lower than 98% as controlled by UV and MALDI-TOF mass spectrometry. The secondary structure was determined in water, trifluoroethanol (TFE) and in lipid membrane using UV circular dichroism. The peptide shows dominant beta-sheeted structures in water that convert progressively into alpha-helical features upon addition of TFE or membrane. The amphipathic character of the helix suggests that the peptide might have a structure akin to those of antimicrobial peptides upon interaction with membranes.