5-HT2 receptor blocker sarpogrelate prevents downregulation of antiapoptotic protein Bcl-2 and protects the heart against ischemia-reperfusion injury

Even though reperfusion is the treatment of choice in patients admitted with acute myocardial infarction, reperfusion itself has been demonstrated to activate various pathological factors especially following procedures of cardiac revascularization. 5-hydroxytryptamine (5HT) is one such factor activated during reperfusion and is known to trigger the post ischemic contractile dysfunction and pathological apoptosis. Here we demonstrate the potential effects of the 5-HT(2)A antagonist sarpogrelate in protecting the myocardium against reperfusion injury of heart. Male Wistar rats weighing between 220 and 240 g were subjected to 30 min left coronary artery (LCA) occlusion and 120 min reperfusion. Sarpogrelate (4 mg/kg) was infused intravenously for 30 min either before LCA occlusion or at reperfusion. Following reperfusion the samples were collected for infarction area, immunohistochemistry, western blotting and myocardial metabolite analysis. Sarpogrelate infusion before ischemia resulted in (a) significant recovery of post ischemic cardiac functions (LVDP, EDP), (b) significant reduction in the infarct size among the risk area after triphenyl tetrazolium chloride staining (p<0.001), (c) decreased tissue water content (p<0.05), (d) well preserved myocardial ATP (p<0.05), (e) reduction in Bcl-2 downregulation and caspase 3 activation and (g) less prevalence of apoptotic cells (3.1+/-0.4% to 15.2+/-0.6%, drug versus control). Treating the rats with sarpogrelate during reperfusion also showed similar results. This study thus demonstrates the protective effects of sarpogrelate and supports the role for 5-HT2A inhibition in preventing the reperfusion injury of the heart.     

Local delivery of soluble TNF-alpha receptor 1 gene reduces infarct size following ischemia/reperfusion injury in rats

Apoptosis in the myocardium is linked to ischemia/reperfusion injury, and TNF-alpha induces apoptosis in cardiomyocytes. A significant amount of TNF-alpha is detected after ischemia and reperfusion. Soluble TNF-alpha receptor 1 (sTNFR1) is an extracellular domain of TNF-alpha receptor 1 and is an antagonist to TNF-alpha. In the present study, we examined the effects of sTNFR1 on infarct size in acute myocardial infarction (AMI) following ischemia/reperfusion. Male Wistar rats were subjected to left coronary artery (LCA) ligation. After 30 min of LCA occlusion, the temporary ligature on the LCA was released and blood flow was restored. Immediately after reperfusion, a total of 200 microg of sTNFR1 or LacZ plasmid was injected into three different sites of the left ventricular wall. At 6 h, 1 and 2 days after reperfusion, the TNF-alpha bioactivity in the myocardium was significantly higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase in the TNF-alpha bioactivity. The sTNFR1 plasmid significantly reduced DNA fragmentation and caspase activity compared to the LacZ plasmid. Finally, the sTNFR1 expression-plasmid treatment significantly reduced the area of myocardial infarction at 2 days after ischemia/reperfusion compared to LacZ plasmid. In conclusion, the TNF-alpha bioactivity in the heart increased from the early stage of ischemia/reperfusion, and this increase was thought to contribute in part to the increased area of myocardial infarction. Suppression of TNF-alpha bioactivity with the sTNFR1 plasmid reduced the infarct size in AMI following ischemia and reperfusion.     

Generalized Make and Use Framework for Allocation in Life Cycle Assessment

Allocation in life cycle inventory (LCI) analysis is one of the long‐standing methodological issues in life cycle assessment (LCA). Discussion on allocation among LCA researchers has taken place almost in complete isolation from the series of closely related discussions from the 1960s in the field of input?output economics, regarding the supply and use framework. This article aims at developing a coherent mathematical framework for allocation in LCA by connecting the parallel developments of the LCA and the input?output communities. In doing so, the article shows that the partitioning method in LCA is equivalent to the industry‐technology model in input?output economics, and system expansion in LCA is equivalent to the by‐product‐technology model in input?output output economics. Furthermore, we argue that the commodity‐technology model and the by‐product‐technology model, which have been considered as two different models in input?output economics for more than 40 years, are essentially equivalent when it comes to practical applications. It is shown that the matrix‐based approach used for system expansion successfully solves the endless regression problem that has been raised in LCA literature. A numerical example is introduced to demonstrate the use of allocation models. The relationship of these approaches with consequential and attributional LCA models is also discussed.     

Considerations and a report on the state of practice

Life Cycle Assessment (LCA) is an analytical tool to evaluate the environmental consequences of products and their production systems. A great deal of effort has been devoted to developing methodology and guidelines for conducting LCAs. However, many companies are devising shortcuts to the full LCA model. We conducted discussions with twenty-one LCA practitioners and researchers to investigate techniques being used to simplify or streamline the LCA methodology. We found a wide variety of approaches being used to accomplish the streamlining from convening informal in-house expert panels to identify life cycle issues to developing and applying formal, structured tools.     

Lifting the veil on the correction of double counting incidents in hybrid life cycle assessment

Life cycle assessment (LCA) and environmentally extended input–output analyses (EEIOA) are two techniques commonly used to assess environmental impacts of an activity/product. Their strengths and weaknesses are complementary, and they are thus regularly combined to obtain hybrid LCAs. A number of approaches in hybrid LCA exist, which leads to different results. One of the differences is the method used to ensure that mixed LCA and EEIOA data do not overlap, which is referred to as correction for double counting. This aspect of hybrid LCA is often ignored in reports of hybrid assessments and no comprehensive study has been carried out on it. This article strives to list, compare, and analyze the different existing methods for the correction of double counting. We first harmonize the definitions of the existing correction methods and express them in a common notation, before introducing a streamlined variant. We then compare their respective assumptions and limitations. We discuss the loss of specific information regarding the studied activity/product and the loss of coherent financial representation caused by some of the correction methods. This analysis clarifies which techniques are most applicable to different tasks, from hybridizing individual LCA processes to integrating complete databases. We finally conclude by giving recommendations for future hybrid analyses.     

Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo

Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death. Deletion of sEH has been shown to be protective against myocardial ischemia in the isolated heart preparation. We tested the hypothesis that sEH inactivation by targeted gene deletion or pharmacological inhibition reduces infarct size (I) after regional myocardial ischemia-reperfusion injury in vivo. Male C57BL\6J wild-type or sEH knockout mice were subjected to 40 min of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 min before LCA occlusion or during ischemia 10 min before reperfusion. 14,15-EET, the main substrate for sEH, was administered intravenously 15 min before LCA occlusion or during ischemia 5 min before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 min before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and triphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15-EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15-EEZE. Immunohistochemistry revealed abundant sEH protein expression in left ventricular tissue. Strategies to increase 14,15-EET, including sEH inactivation, may represent a novel therapeutic approach for cardioprotection against myocardial ischemia-reperfusion injury.     

Characterizing,Propagating, and Analyzing Uncertainty in Life‐Cycle Assessment: A Survey of Quantitative Approaches

Life‐cycle assessment (LCA) practitioners build models to quantify resource consumption, environmental releases, and potential environmental and human health impacts of product systems. Most often, practitioners define a model structure, assign a single value to each parameter, and build deterministic models to approximate environmental outcomes. This approach fails to capture the variability and uncertainty inherent in LCA. To make good decisions, decision makers need to understand the uncertainty in and divergence between LCA outcomes for different product systems. Several approaches for conducting LCA under uncertainty have been proposed and implemented. For example, Monte Carlo simulation and fuzzy set theory have been applied in a limited number of LCA studies. These approaches are well understood and are generally accepted in quantitative decision analysis. But they do not guarantee reliable outcomes. A survey of approaches used to incorporate quantitative uncertainty analysis into LCA is presented. The suitability of each approach for providing reliable outcomes and enabling better decisions is discussed. Approaches that may lead to overconfident or unreliable results are discussed and guidance for improving uncertainty analysis in LCA is provided.     

Cold reactive lymphocytotoxic antibodies in pulmonary tuberculosis: correlation with disease activity and HLA

Cold reactive lymphocytotoxic antibodies (LCA) are more reactive in cold than at 37 degrees C and occur following infection, immunization or vaccination and in various autoimmune diseases. In the present study, LCA activity against T and B-lymphocytes has been investigated in patients with pulmonary tuberculosis (PTB), their various clinical sub-groups and consanguineous relatives. Further, the relevance of HLA factors in LCA activity was analyzed. The sera from 144 PTB patients, 52 family contacts and 52 healthy individuals were tested for presence of LCAs by a modified two-stage NIH microlymphocytotoxicity assay. A significant increase in LCA activity against both T (32.6% vs 5.7%, P < 0.0001) and B (59.7% vs 13.4%, P < 0.0000001) cells was observed in PTB patients as compared to healthy controls. There was no correlation between serum LCA activity and sputum acid-fast bacilli status. However, only B cell LCAs revealed significant increase in parallel to disease advancement as assessed by X-ray chest examination. Further, LCA activity was more pronounced in drug responders than drug failure group of patients. No significant difference in the distribution of HLA class I and class II antigens was observed between LCA positive and LCA negative patients. However, panel cells carrying HLA-A1, -A11 and -DR3 were often found reactive in LCA positive patient sera. In household family contacts, LCAs were significantly increased only against B cells as compared to healthy controls (38.4% vs 13.4%, P < 0.01). This study suggests that Mycobacterium tuberculosis infection/exposure could account for the occurrence of LCAs in pulmonary tuberculosis and the strength of these antibodies is related to disease severity and the extent of lung involvement.     

Possibility Theory: A New Approach to Uncertainty Analysis? (3 pp)

Background, Aims and Scope The problem of the evaluation of practitioner's belief and belief-related uncertainties on LCA results obtained from different methodological choices has been addressed so far by scenario modeling, Cultural Theory perspectives and probabilistic simulation. The direct evaluation of belief and related uncertainties could be of interest, e.g. when the information available (resulting from classical uncertainty analysis or the application of the precautionary principle) do not allow one to choose between methodological alternatives leading to different LCA results and conclusions. The difficulty of modeling belief arises from the additive nature of classical measures, e.g. probabilities. Since the 1960s, non-additive measures (e.g. possibilities) have been developed and applied to model belief in real world problems. The aim of this paper is to discuss the application of possibility measures in LCA for uncertainty analysis in complement to classical approaches. Methods The nature and the meaning of possibilities are briefly introduced by comparison with probabilities (subjective or not) in order to enlighten strengths, drawbacks and complementarities. A tentative possibilistic approach based on the evaluation of a posteriori possibilities of final LCA results depending on a priori possibilities of the methodological choices behind the calculations is described, also by means of an application example. Results and Outlook. A new approach for the modeling of practitioner's belief and belief-related uncertainties in complement of classical methods of uncertainty analysis has been proposed for discussion. Uncertainty can be characterized by confidence intervals and indexes that could help practitioners in making methodological choices and could improve the interpretation and reliability of LCA results, still increasing its sophistication.     

Life cycle assessment in the minerals and metals sector: a critical review of selected issues and challenges

Background, aim and scope

The mining sector provides materials that are essential elements in a wide range of goods and services, which create value by meeting human needs. Mining and processing activities are an integral part of most complex material cycles so that the application of life cycle assessment (LCA) to minerals and metals has therefore gained prominence. In the past decade, increased use of LCA in the mineral and metal sector has advanced the scientific knowledge through the development of scientifically valid life cycle inventory databases. Though scientifically valid, LCA still needs to depend on several technical assumptions. In particular, measuring the environmental burden issues related to abiotic resource depletion, land use impacts and open-loop recycling within the LCA are widely debated issues. Also, incorporating spatial and temporal sensitivities in LCA, to make it a consistent scientific tool, is yet to be resolved. This article discusses existing LCA methods and proposed models on different issues in relation to minerals and metals sector.

Main features

A critical review was conducted of existing LCA methods in the minerals and metals sector in relation to allocation issues related to indicators of land use impacts, abiotic resource depletion, allocation in open-loop recycling and the system expansions and accounting of spatial and temporal dimension in LCA practice.

Results

Evolving a holistic view about these contentious issues will be presented with view for future LCA research in the minerals and metals industry. This extensive literature search uncovers many of the issues that require immediate attention from the LCA scientific community.

Discussion

The methodological drawbacks, mainly problems with inconsistencies in LCA results for the same situation under different assumptions and issues related to data quality, are considered to be the shortcomings of current LCA. In the minerals and metals sector, it is important to increase the objectivity of LCA by way of fixing those uncertainties, for example, in the LCA of the minerals and metals sector, whether the land use has to be considered in detail or at a coarse level. In regard to abiotic resource characterisation, the weighting and time scales to be considered become a very critical issue of judgement. And, in the case of open-loop recycling, which model will best satisfy all the stake holders? How the temporal and spatial dimensions should be incorporated into LCA is one of the biggest challenges ahead of all those who are concerned. Addressing these issues shall enable LCA to be used as a policy tool in environmental decision-making. There has been enormous debate with respect to on land use impacts, abiotic resource depletion, open-loop recycling and spatial and temporal dimensions, and these debates remain unresolved. Discussions aimed at bringing consensus amongst all the stake holders involved in LCA (i.e. industry, academia, consulting organisations and government) will be presented and discussed. In addition, a commentary of different points of view on these issues will be presented.

Conclusions

This review shall bring into perspective some of those contentious issues that are widely debated by many researchers. The possible future directions proposed by researchers across the globe shall be presented. Finally, authors conclude with their views on the prospects of LCA for future research endeavours.

Recommendations and outlook

Specific LCA issues of minerals and metals need to be investigated further to gain more understanding. To facilitate the future use of LCA as a policy tool in the minerals and metals sector, it is important to increase the objectivity with more scientific validity. Therefore, it is essential that the issues discussed in this paper are addressed to a great detail.     

Effect of the new anti-arrhythmia preparation Bonnecor on the hemodynamics and activity of the ischemic heart

The effect of newly-developed anti-arrhythmia drug Bonnecor compared to that of ethacizin and lidocaine has been studied on anesthetized rats under acute myocardial ischemia. The drugs injected intravenously prior to coronary artery occlusion have been shown to prevent to a great degree the appearance of hemodynamic and functional disturbances of the heart. When compared to control, less reduction in systemic arterial pressure, systolic discharge cardiac output, contractility and heart power were observed. In addition, Bonnecor has been found to have certain advantages over reference drugs.     

Effect of certain lectins on platelet aggregation in healthy people

A study was made of the ability of some plant lectins, which bind specifically to different carbohydrate determinants of glycoproteins, to induce the platelet aggregation in healthy humans. It has been shown that phytohemagglutinin (PHA) and wheat germ agglutinin (MGA) induce a more marked platelet aggregation than concanvalin A (Con A). Lens culinaris agglutinin (LCA) had a slight aggregate activity. It was pointed at different roles played by carbohydrate determinants of platelet glycoproteins in fulfilling their aggregation function.     

Effect of the beta-adrenoblockader atenolol on the extent of myocardial necrosis in transient and permanent coronary occlusion

It has been demonstrated in experiments on rats that atenolol in a dose of 10 mg/kg exerts an antiischemic action in transitory coronary occlusion lasting 30 minutes followed by reperfusion for 23h and 30 min. The effect manifested in the diminution of the relative area and mass of myocardial necrosis zone and in the dilatation of the left ventricle. Atenolol also produced an antiischemic action in permanent coronary occlusion for 24 h. However, the effect in the latter case was less marked than in transitory occlusion. When injected for permanent occlusion, atenolol (10 mg/kg i. v.) led to a 1.59-fold decrease in the necrosis area and a 2.1-fold decrease (p less than 0.001) when administered for transitory occlusion. The mass of the myocardial necrosis zone also dropped (by 1.65-fold and 2.3-fold, respectively), whereas the degree of dilatation by 2.1- and 2.3-fold, respectively.     

Status update on LCA studies and networking in Tanzania

Purpose

Life cycle assessment (LCA) has become a standard for assessing what impacts do products and/or services have throughout their entire life cycle. Since the inception of LCA technique, studies have been conducted in different parts of the world, including Tanzania. This study describes the current status of LCA, capacities, and networking in Tanzania. The study has identified what has already been done and potential research gaps that could be explored in future LCA studies.

Methods

A state-of-the-art review was conducted on published articles, reports, and other materials on LCA in Tanzania (covering a time frame of 1990–2015) which were searched on databases of scientific research and the general internet using a combination of keywords: “life cycle assessment and Tanzania,” “LCA and Tanzania,” and “life cycle assessment and LCA and Tanzania.” Reviews were on current status, research gaps, and the need for future research. Information related to education or training activities and networking were also gathered and reviewed.

Results and discussion

Literature review has revealed that in Tanzania the first LCA study was published in 2007. Few articles and reports were identified in which LCA technique was used mainly for academic research in agriculture, electricity generation, charcoal, biodiesel production from jatropha oil, bioethanol production from sugarcane molasses, production of biofuels from pyrolysis of wood, and production of charcoal from sawmill residues. The very small number of LCA studies conducted in the country could be due to the lack of skilled personnel, lack of local data, and lack of research funds. Tanzania Life Cycle Assessment Network was created to link LCA practitioners and to promote and support further development of LCA in the country. Also, LCA potential is huge yet to be fully explored.

Conclusions

This state-of-the-art review is the first of its kind that summarizes and puts together all LCA studies in Tanzania. Most studies faced the challenge of lack of local data, which resulted to the use of secondary data from the literature. In LCA, the use of data from different geographical conditions could cause bias of the results and consequently could affect the decision made or to be made from the study. In this regard, the study recommends the establishment of national LCI database to solve this problem. Also, most studies covered only few impact categories prompting for full LCA studies in future studies. The study also found that there is a need to establish regular LCA training and courses for capacity development.

     

Comparison of lectin-binding patterns between young adult and older rat glycoproteins in the brain

Glycoproteins in the soluble fraction and in the membrane fraction of various portions of brains and spinal cords, obtained from 9-week-old rats and 29-month-old rats, were comparatively analyzed by SDS-polyacrylamide gel electrophoresis and lectin staining. The glycoprotein patterns of each brain part showed marked differences by the age of donors. The most prominent evidence in the soluble fractions of white matter, basal ganglia, and spinal cord detected by WGA is that the glycoproteins with an apparent molecular weight of 123K and 115K have increased in the aged rats. In addition, the reactivity of 115K with Con A and PNA has also increased in the aged rats. On the other hand, reactivity of an apparent molecular weight of 115K with WGA has increased in the membrane fractions of white matter, basal ganglia, hippocampus, cerebellum, and spinal cord from the aged rats. In contrast, by MAM, which is specific for Sia2®3Gal linkage, an apparent molecular weight of 115K has been detected only in the membrane fraction of cerebellum and it has decreased in the aged rats. Reactivity of an apparent molecular weight of 133K and 125K in the membrane fractions of white matter and basal ganglia with LCA has decreased in the aged rats. In contrast, reactivity of the front band with LCA and AAL has increased and that of 130K with AAL has decreased in spinal cord from the aged rats, respectively. These results indicate that the glycosylation state of the protein in the brain changes during aging.     

Functional and morphological basis for the nature of the microcirculatory bed reactions of the bulbar conjunctiva in experimental occlusion of the cranial mesenteric artery

A complex analysis on changes occurring in conjunctival microcirculation and a number of indices of hemodynamics, hemorheology and metabolism at different time of experimental occlusion in the cranial mesenteric artery has demonstrated certain objective and many-sided correlations that prove a systemic character of biomicroscopical changes in the conjunctiva. The degree of changes in the conjunctival microcirculation depends on duration of occlusion. After a 3 hours' occlusion revascularization is accompanied by reversible general microcirculatory disorders that are registered in bulboconjunctiva. In a 6 and 12 hours' occlusion revascularization is characterized by increasing general changes in microcirculation.     

CvP-bias as an index to predict the life style of last common ancestor

CvP-bias (difference between proportions of charged and polar non-charged amino acids) has been recognized as an efficient criterion to distinguish hyperthermophiles from mesothermophiles. By analyzing the CvP-biases of seven barophiles's proteomes, we reveal that this criterion still works for barophiles. As a result, CvP-bias criterion is applicable to disclosing some secrets in the lifestyles of the last common ancestor (LCA), no matter the LCA lived in deep sea or not, which is helpful to building a self-consistent model for the LCA.     

6th SETAC-Europe Meeting: LCA - Selected Papers uses

Most former methods for the impact assessment of toxic releases in LCA gave a relative yardstick for the potential toxic effect of a substance, with no allowance being made for intermedia transport and degradation. These factors may be of major influence on the degree of (eco)toxic effects to be expected. As part of its work on substance policy, RIVM has developed a computer model calledUniform System for the Evaluation of Substances (USES) to assess, as realistically as possible, the degree to which the no-effect level is transgressed in practice. This model makes allowances for the fate of substances in the environment. An important offspring of the project is not only that substance assessment has been linked to the LCA method, but also that it shows LCA users how they can establish the LCA equivalency factors for the (eco)toxicity of “unknown” substances by themselves, and how they can recalculate the equivalency factors that were reported from the project. This last point is particularly of interest because the new list of equivalency factors suffers from serious uncertainties due to data gaps. Lastly, some future perspectives as to further modelling activities is discussed, in particular with respect to a generic fate model for all emission-related impact types.     

Three-dimensional structural model analysis of the binding site of lithocholic acid, an inhibitor of DNA polymerase beta and DNA topoisomerase II.

The molecular action of lithocholic acid (LCA), a selective inhibitor of mammalian DNA polymerase beta (pol beta), was investigated. We found that LCA could also strongly inhibit the activity of human DNA topoisomerase II (topo II). No other DNA metabolic enzymes tested were affected by LCA. Therefore, LCA should be classified as an inhibitor of both pol beta and topo II. Here, we report the molecular interaction of LCA with pol beta and topo II. By three-dimensional structural model analysis and by comparison with the spatial positioning of specific amino acids binding to LCA on pol beta (Lys60, Leu77, and Thr79), we obtained supplementary information that allowed us to build a structural model of topo II. Modeling analysis revealed that the LCA-interaction interface in both enzymes has a pocket comprised of three amino acids in common, which binds to the LCA molecule. In topo II, the three amino acid residues were Lys720, Leu760, and Thr791. These results suggested that the LCA binding domains of pol beta and topo II are three-dimensionally very similar.