Fluxes of Copper-Complexing Ligands from Estuarine Sediments

Most studies of the organic complexation of Cu in natural waters have focused on distributions and processes in the water column, where a significant fraction of Cu-complexing ligands may be biologically produced. We present direct evidence for a flux of Cu-complexing ligands from estuarine sediments, demonstrating that sediments are a significant, yet previously unrecognized source of the ligands. Fluxes of Cu-complexing ligands from Chesapeake Bay sediments range from 300 to 1,200 nmol m-2 d-1, exceeding fluxes of total dissolved Cu by 3-\u3e40-fold, suggesting that any Cu fluxing from the sediments is likely to be organically complexed. Our results indicate that benthic fluxes may supply from 10 to 50% of the standing stock of Cu-complexing ligands in Chesapeake Bay and suggest that such fluxes may strongly influence the biogeochemistry of Cu in shallow water environments and potentially in the ocean as a whole

Circulating endothelial cells demonstrate an attenuation of endothelial damage by minimizing the extracorporeal circulation

ObjectiveDetachment of endothelial cells may represent serious injury of the endothelium after cardiopulmonary bypass. We investigated whether the extent of endothelial injury is related to the type of cardiopulmonary bypass system used (conventional or minimized) and determined circulating endothelial cells as well as von Willebrand factor and soluble thrombomodulin.MethodsTwenty patients scheduled for elective coronary bypass grafting were randomly assigned to either the minimal extracorporeal circulation system or the standard cardiopulmonary bypass. Ten healthy volunteers served as controls. Circulating endothelial cells per milliliter of full blood were perioperatively determined by immunomagnetic cell separation technique. Endothelial plasma markers were measured by enzyme-linked immunosorbent assay.ResultsPreoperative circulating endothelial cell numbers did not differ between the experimental groups, but were significantly higher than in the healthy controls (18.6 ± 5.6 vs 7.2 ± 3.8, P < .001). At 6 hours, circulating endothelial cell numbers increased significantly compared with baseline in both experimental groups and peaked at 12 hours after cardiopulmonary bypass initiation, each time with significantly lower values in the minimal extracorporeal circulation group (6 hours: 44.0 ± 9.9 vs 29.6 ± 9.8, P = .007; 12 hours: 48.1 ± 6.8 vs 31.8 ± 7.1, P < .001). Likewise, von Willebrand factor and soluble thrombomodulin postoperatively increased in both groups with a tendency toward lower levels in the minimal extracorporeal circulation group. Although circulating endothelial cells gradually declined, continually with lower numbers in the minimal extracorporeal circulation group, the endothelial plasma markers remained elevated during observation time.ConclusionsCirculating endothelial cells represent a novel marker of the intrinsic endothelial damage caused by cardiopulmonary bypass. Its analysis facilitates the evaluation of cardiopulmonary bypass modifications as the minimal extracorporeal circulation system could be proven to be less injurious to endothelium and myocardium

Lifestyle Medicine-Related Cardiovascular Risk Factor Changes in Employees Participating in a Pharmacist-Run Risk Reduction Program

Cardiovascular disease (CVD) remains the leading cause of death among American adults accounting for approximately one-third of all deaths. It has been shown, however, that the actual causes of death are related to lifestyle behaviors such as tobacco use, poor diet and physical activity and alcohol consumption. A pharmacist-run employee health program, started in 2008, sought to lower CVD risk through the use of individualized lifestyle behavior programming, medication therapy management, and care coordination activities. Following one year of participation in the program, employee participants were shown to significantly increase exercise quantity (p < 0.001), fruit and vegetable consumption (p < 0.001), and decrease self-reported stress level (p = 0.006). The percentage of program participants simultaneously adherent to the recommended levels of exercise, combined fruit and vegetable intake and tobacco abstinence at one-year was 34.5% vs. 5.5% at baseline. This compares with only 5.1% of the U.S. population adherent to the same three behaviors. Pharmacists can positively impact healthy lifestyle behaviors when working in an employee health setting

Literatur

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Effect of closed minimized cardiopulmonary bypass on cerebral tissue oxygenation and microembolization

ObjectiveCoronary artery bypass grafting with cardiopulmonary bypass carries a risk for neurologic complications because of cerebral hypoperfusion and microembolization. The basic goals of a novel closed minimized extracorporeal circulation are to prevent excessive hemodilution and to avoid blood-air interface. The aim of this prospective randomized study was to determine the effect of using the minimized extracorporeal circulation system compared with open conventional extracorporeal circulation on cerebral tissue oxygenation and microembolization.MethodsForty patients undergoing coronary artery bypass grafting (20 in each group) were continuously monitored for changes in cerebral oxygenated hemoglobin and tissue oxygenation index by using near-infrared spectroscopy. Total microembolic count and gaseous embolic count in both median cerebral arteries were monitored with multifrequency transcranial Doppler instrumentation.ResultsIn the conventional extracorporeal circulation group there was a highly significant reduction in both cerebral oxygenated hemoglobin and tissue oxygenation index from the start to the end of cardiopulmonary bypass (P < .01). The rate of decrease in cerebral oxygenated hemoglobin after aortic cannulation was faster in the conventional extracorporeal circulation group (F test = 9.03, P < .001). No significant changes with respect to cerebral oxygenated hemoglobin or tissue oxygenation index occurred in the minimized extracorporeal circulation group, except at the beginning of rewarming (P < .01). Total embolic count, as well as gaseous embolic count, in the left and right median cerebral arteries was significantly lower in the minimized extracorporeal circulation group (all P < .05). Postoperative bleeding was greater (P < .05) and the transfusion rate was higher (P < .05) in the conventional extracorporeal circulation group.ConclusionsUse of closed minimized cardiopulmonary bypass compared with conventional open cardiopulmonary bypass preserves cerebral tissue oxygenation and reduces cerebral microembolization

Coronary artery surgery: cardiotomy suction or cell salvage?

Coronary artery bypass grafting (CABG) today results in what may be regarded as acceptable levels of blood loss with many institutions avoiding allogeneic red cell transfusion in over 60% of their patients. The majority of cardiac surgeons employ cardiotomy suction to preserve autologous blood during on-pump coronary artery bypass surgery; however the use of cardiotomy suction is associated with a more pronounced systemic inflammatory response and a resulting coagulopathy as well as exacerbating the microembolic load. This leads to a tendency to increased blood loss, transfusion requirement and organ dysfunction. Conversely, the avoidance of cardiotomy suction in coronary artery bypass surgery is not associated with an increased transfusion requirement. There is therefore no indication for the routine use of cardiotomy suction in on-pump coronary artery surgery

Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa

<p>Abstract</p> <p>Background</p> <p>HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype-specific differences in the appearance of CXCR4 tropism late in disease.</p> <p>Results</p> <p>We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60-77%), except for subtype C (15%).</p> <p>Conclusions</p> <p>The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens.</p

Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes

Human immunodeficiency virus type 1 (HIV-1) tropism can be assessed using phenotypic assays, but this is quite laborious, expensive, and time-consuming and can be made only in sophisticated laboratories. More accessible albeit reliable tools for testing of HIV-1 tropism are needed in view of the prompt introduction of CCR5 antagonists in clinical practice. Bioinformatics tools based on V3 sequences might help to predict HIV-1 tropism; however, most of these methods have been designed by taking only genetic information derived from HIV-1 subtype B into consideration. The aim of this study was to evaluate the performances of several genotypic tools to predict HIV-1 tropism in non-B subtypes, as data on this issue are scarce. Plasma samples were tested using a new phenotypic tropism assay (Phenoscript-tropism; Eurofins), and results were compared with estimates of coreceptor usage using eight different genotypic predictor softwares (Support Vector Machine [SVM], C4.5, C4.5 with positions 8 to 12 only, PART, Charge Rule, geno2pheno coreceptor, Position-Specific Scoring Matrix X4R5 [PSSMX4R5], and PSSMsinsi). A total of 150 samples were tested, with 115 belonging to patients infected with non-B subtypes and 35 drawn from subtype B-infected patients, which were taken as controls. When non-B subtypes were tested, the concordances between the results obtained using the phenotypic assay and distinct genotypic tools were as follows: 78.8% for SVM, 77.5% for C4.5, 82.5% for C4.5 with positions 8 to 12 only, 82.5% for PART, 82.5% for Charge Rule, 82.5% for PSSMX4R5, 83.8% for PSSMsinsi, and 71.3% for geno2pheno. When clade B viruses were tested, the best concordances were seen for PSSMX4R5 (91.4%), PSSMsinsi (88.6%), and geno2pheno (88.6%). The sensitivity for detecting X4 variants was lower for non-B than for B viruses, especially in the case of PSSMsinsi (38.4% versus 100%, respectively), SVMwetcat (46% versus 100%, respectively), and PART (30% versus 90%, respectively). In summary, while inferences of HIV-1 coreceptor usage using genotypic tools seem to be reliable for clade B viruses, their performances are poor for non-B subtypes, in which they particularly fail to detect X4 variants

A Functional Proteomic Method for Biomarker Discovery

The sequencing of the human genome holds out the hope for personalized medicine, but it is clear that analysis of DNA or RNA content alone is not sufficient to understand most disease processes. Proteomic strategies that allow unbiased identification of proteins and their post-transcriptional and -translation modifications are an essential complement to genomic strategies. However, the enormity of the proteome and limitations in proteomic methods make it difficult to determine the targets that are particularly relevant to human disease. Methods are therefore needed that allow rational identification of targets based on function and relevance to disease. Screening methodologies such as phage display, SELEX, and small-molecule combinatorial chemistry have been widely used to discover specific ligands for cells or tissues of interest, such as tumors. Those ligands can be used in turn as affinity probes to identify their cognate molecular targets when they are not known in advance. Here we report an easy, robust and generally applicable approach in which phage particles bearing cell- or tissue-specific peptides serve directly as the affinity probes for their molecular targets. For proof of principle, the method successfully identified molecular binding partners, three of them novel, for 15 peptides specific for pancreatic cancer