15 research outputs found
The influence of a solvent environment on direct non-covalent interactions between two molecules: A symmetry-adapted perturbation theory study of polarization tuning of π-π interactions by water
No full textHigh-level quantum chemical computations have provided significant insight into the fundamental physical nature of non-covalent interactions. These studies have focused primarily on gas-phase computations of small van der Waals dimers; however, these interactions frequently take place in complex chemical environments, such as proteins, solutions, or solids. To better understand how the chemical environment affects non-covalent interactions, we have undertaken a quantum chemical study of π-π interactions in an aqueous solution, as exemplified by T-shaped benzene dimers surrounded by 28 or 50 explicit water molecules. We report interaction energies (IEs) using second-order Møller-Plesset perturbation theory, and we apply the intramolecular and functional-group partitioning extensions of symmetry-adapted perturbation theory (ISAPT and F-SAPT, respectively) to analyze how the solvent molecules tune the π-π interactions of the solute. For complexes containing neutral monomers, even 50 explicit waters (constituting a first and partial second solvation shell) change total SAPT IEs between the two solute molecules by only tenths of a kcal mol-1, while significant changes of up to 3 kcal mol-1 of the electrostatic component are seen for the cationic pyridinium-benzene dimer. This difference between charged and neutral solutes is attributed to large non-additive three-body interactions within solvated ion-containing complexes. Overall, except for charged solutes, our quantum computations indicate that nearby solvent molecules cause very little tuning of the direct solute-solute interactions. This indicates that differences in binding energies between the gas phase and solution phase are primarily indirect effects of the competition between solute-solute and solute-solvent interactions
Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation.
No full textBackground Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. Objectives To determine the most effective use of platelet transfusion for the prevention of bleeding in patients with haematological disorders undergoing chemotherapy or stem cell transplantation. Search methods This is an update of a Cochrane review first published in 2004. W e searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2011), MEDLINE (1950 to Nov 2011), EMBASE (1980 to Nov 2011) and CINAHL (1982 to Nov 2011), using adaptations of the Cochrane RCT search filter, the UKBTS/SRI Transfusion Evidence Library, and ongoing trial databases to 10 November 2011. Selection criteria RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients with haematological disorders. Four different types of prophylactic platelet transfusion trial were included Data collection and analysis In the original review one author initially screened all electronically derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two authors performed this task in the updated review. Two authors independently assessed the full text of all potentially relevant trials for eligibility. Two authors completed data extraction independently. We requested missing data from the original investigators as appropriate
Pathogen-reduced platelets for the prevention of bleeding.
No full textBACKGROUND: Platelet transfusions are used to prevent and treat bleeding in patients who are thrombocytopenic. Despite improvements in donor screening and laboratory testing, a small risk of viral, bacterial or protozoal contamination of platelets remains. There is also an ongoing risk from newly emerging blood transfusion-transmitted infections (TTIs) for which laboratory tests may not be available at the time of initial outbreak.One solution to reduce further the risk of TTIs from platelet transfusion is photochemical pathogen reduction, a process by which pathogens are either inactivated or significantly depleted in number, thereby reducing the chance of transmission. This process might offer additional benefits, including platelet shelf-life extension, and negate the requirement for gamma-irradiation of platelets. Although current pathogen-reduction technologies have been proven significantly to reduce pathogen load in platelet concentrates, a number of published clinical studies have raised concerns about the effectiveness of pathogen-reduced platelets for post-transfusion platelet recovery and the prevention of bleeding when compared with standard platelets. OBJECTIVES: To assess the effectiveness of pathogen-reduced platelets for the prevention of bleeding in patients requiring platelet transfusions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 1), MEDLINE (1950 to 18 February 2013), EMBASE (1980 to 18 February 2013), CINAHL (1982 to 18 February 2013) and the Transfusion Evidence Library (1980 to 18 February 2013). We also searched several international and ongoing trial databases and citation-tracked relevant reference lists. We requested information on possible unpublished trials from known investigators in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the transfusion of pathogen-reduced platelets with standard platelets. We did not identify any RCTs which compared the transfusion of one type of pathogen-reduced platelets with another. DATA COLLECTION AND ANALYSIS: One author screened all references, excluding duplicates and those clearly irrelevant. Two authors then screened the remaining references, confirmed eligibility, extracted data and analysed trial quality independently. We requested and obtained a significant amount of missing data from trial authors. We performed meta-analyses where appropriate using the fixed-effect model for risk ratios (RR) or mean differences (MD), with 95% confidence intervals (95% CI), and used the I² statistic to explore heterogeneity, employing the random-effects model when I² was greater than 30%. MAIN RESULTS: We included 10 trials comparing pathogen-reduced platelets with standard platelets. Nine trials assessed Intercept® pathogen-reduced platelets and one trial Mirasol® pathogen-reduced platelets. Two were randomised cross-over trials and the remaining eight were parallel-group RCTs. In total, 1422 participants were available for analysis across the 10 trials, of which 675 participants received Intercept® and 56 Mirasol® platelet transfusions. Four trials assessed the response to a single study platelet transfusion (all Intercept®) and six to multiple study transfusions (Intercept® (N = 5), Mirasol® (N = 1)) compared with standard platelets.We found the trials to be generally at low risk of bias but heterogeneous regarding the nature of the interventions (platelet preparation), protocols for platelet transfusion, definitions of outcomes, methods of outcome assessment and duration of follow-up.Our primary outcomes were mortality, 'any bleeding', 'clinically significant bleeding' and 'severe bleeding', and were grouped by duration of follow-up: short (up to 48 hours), medium (48 hours to seven days) or long (more than seven days). Meta-analysis of data from five trials of multiple platelet transfusions reporting 'any bleeding' over a long follow-up period found an increase in bleeding in those receiving pathogen-reduced platelets compared with standard platelets using the fixed-effect model (RR 1.09, 95% CI 1.02 to 1.15, I² = 59%); however, this meta-analysis showed no difference between treatment arms when using the random-effects model (RR 1.14, 95% CI 0.93 to 1.38).There was no evidence of a difference between treatment arms in the number of patients with 'clinically significant bleeding' (reported by four out of the same five trials) or 'severe bleeding' (reported by all five trials) (respectively, RR 1.06, 95% CI 0.93 to 1.21, I² = 2%; RR 1.27, 95% CI 0.76 to 2.12, I² = 51%). We also found no evidence of a difference between treatment arms for all-cause mortality, acute transfusion reactions, adverse events, serious adverse events and red cell transfusion requirements in the trials which reported on these outcomes. No bacterial transfusion-transmitted infections occurred in the six trials that reported this outcome.Although the definition of platelet refractoriness differed between trials, the relative risk of this event was 2.74 higher following pathogen-reduced platelet transfusion (RR 2.74, 95% CI 1.84 to 4.07, I² = 0%). Participants required 7% more platelet transfusions following pathogen-reduced platelet transfusion when compared with standard platelet transfusion (MD 0.07, 95% CI 0.03 to 0.11, I² = 21%), although the interval between platelet transfusions was only shown to be significantly shorter following multiple Intercept® pathogen-reduced platelet transfusion when compared with standard platelet transfusion (MD -0.51, 95% CI -0.66 to -0.37, I² = 0%). In trials of multiple pathogen-reduced platelets, our analyses showed the one- and 24-hour count and corrected count increments to be significantly inferior to standard platelets. However, one-hour increments were similar in trials of single platelet transfusions, although the 24-hour count and corrected count increments were again significantly lower. AUTHORS' CONCLUSIONS: We found no evidence of a difference in mortality, 'clinically significant' or 'severe bleeding', transfusion reactions or adverse events between pathogen-reduced and standard platelets. For a range of laboratory outcomes the results indicated evidence of some benefits for standard platelets over pathogen-reduced platelets. These conclusions are based on data from 1422 patients included in 10 trials. Results from ongoing or new trials are required to determine if there are clinically important differences in bleeding risk between pathogen-reduced platelet transfusions and standard platelet transfusions. Given the variability in trial design, bleeding assessment and quality of outcome reporting, it is recommended that future trials apply standardised approaches to outcome assessment and follow-up, including safety reporting
Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders
No full textBackground
People with haematological disorders are frequently at risk of severe or life‐threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life‐threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013.
Objectives
To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders.
Search methods
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016.
Selection criteria
We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA.
Data collection and analysis
Two review authors independently screened all electronically‐derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta‐analyses because of the heterogeneity of the available data.
Main results
We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA.
Of the four completed studies, one cross‐over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.
Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity.
We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low‐quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) ‐0.37 to 3.77: consolidation; 18 participants; MD ‐1.50 bleeding events, 95% CI ‐3.25 to 0.25; very low‐quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies.
Two studies reported thromboembolism and no events occurred (68 participants, very low‐quality evidence).
All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low‐quality evidence), but this was reported in different ways and no meta‐analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD ‐5.60 platelet units, 95% CI ‐9.02 to ‐2.18: induction; 38 participants, MD ‐1.00 platelet units, 95% CI ‐9.11 to 7.11; very low‐quality evidence).
Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low‐quality evidence).
None of the studies reported on the following pre‐specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL).
Authors' conclusions
Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020
The safety and effectiveness of different methods of ear wax removal: a systematic review and economic evaluation
No full textEar wax (cerumen) is a natural secretion produced to protect the inner ear from dirt and other fragments by moving these particles towards the outer ear. If this process does not happen properly, wax may build up causing blockage in the ear canal and the possibility of impaction. People with a build up of ear wax may suffer from hearing loss, discomfort and, on occasions, infection. It may present problems in assessing hearing, blocking the view of the ear drum during medical examination and interfering with the fitting or function of hearing aids. Although it is thought to affect between 2% and 6% of the population in the England and Wales, some groups may be at a higher risk, such as those using hearing aids or with small ear canals and/or skin conditions. Recurrence is thought to be high among some of these groups. The consequences of the build up of ear wax in the ear canal are thought to be a common reason for consultation and cost in general practice with over 2 million consultations per year in the NHS.Methods of removal of ear wax include drops, flushing with water in general practice, and removal with suction or probes in specialist clinics. The relative safety and benefits of these different methods of removal remains uncertain. This research will systematically review published and unpublished evidence on the clinical and cost effectiveness of different methods for the removal of ear wax. Where appropriate, it will develop an economic model using data from this systematic review and other relevant sources to estimate the relative costs and benefits of different methods. In addition, the project will provide recommendations for future research to try to help answer any remaining areas of uncertainty
Antifibrinolytics (lysine analogues) for the prevention of bleeding in patients with haematological malignancies (Review).
No full textBackground Patients with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia. This is despite the routine use of prophylactic platelet transfusions (PlTx) to prevent bleeding once the platelet count falls below a certain threshold. PlTx are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic PlTxs is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in patients with haematological disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL Issue 12, 2012), MEDLINE (1948 to 10 January 2013), EMBASE (1980 to 10 January 2013), CINAHL (1982 to 10 January 2013), PubMed (e-publications only) and the Transfusion Evidence Library (1980 to January 2013). We also searched several international and ongoing trial databases to 10 January 2013 and citation-tracked relevant reference lists. Selection criteria RCTs involving patients with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. Data collection and analysis Two authors independently screened all electronically derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. Main results Of 470 articles initially identified, 436 were excluded on the basis of the title and abstract. We reviewed 34 full-text articles from which four studies reported in five articles were eligible for inclusion. We did not identify any RCTs which compared TXA with EACA. We did not identify any ongoing RCTs. One cross-over TXA study (eight patients) was excluded from the outcome analysis because data from this study were at a high risk of bias. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology. Three studies (two TXA (12 to 56 patients), one EACA (18 patients)) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All studies reported bleeding, but it was reported in different ways. All three studies suggested antifibrinolytics reduced the risk of bleeding. The first study showed a difference in average bleeding score of 42 in placebo (P) versus three (TXA). The second study only showed a difference in bleeding episodes during consolidation chemotherapy, with a mean of 2.6 episodes/patient (standard deviation (SD) 2.2) (P) versus a mean of 1.1 episodes/patient (SD 1.4) (TXA). The third study reported bleeding on 50% of days at risk (P) versus bleeding on 31% of days at risk (EACA). Two studies (68 patients) reported thromboembolism and no events occurred. All three studies reported a reduction in PlTx usage. The first study reported a difference of 222 platelet units (P) versus 69 platelet units (TXA). The second study only showed a difference in total platelet usage during consolidation chemotherapy, with a mean of 9.3 units (SD 3.3) (P) versus 3.7 (SD 4.1) (TXA). The third study reported one PlTx every 10.5 days at risk (P) versus one PlTx every 13.3 days at risk (EACA). Two studies reported red cell transfusion requirements and one study found a reduction in red cell transfusion usage. One study reported death due to bleeding as an outcome measure and none occurred. Only one study reported adverse events of TXA as an outcome measure and none occurred. None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). Authors' conclusions Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The only available data suggest that TXA and EACA may be useful adjuncts to platelet transfusions so that platelet use, and the complications associated with their use, can be reduced. However, the trials were too small to assess whether antifibrinolytics increased the risk of thromboembolic events. Large, high-quality RCTs are required before antifibrinolytics can be demonstrated to be efficacious and safe in widespread clinical practice
Cannabinoid CB1 receptor ligand binding and function examined through mutagenesis studies of F200 and S383
No full textSelection of Sustainable Short-Span Bridge Design in Brazil
No full text[EN] Owing to the elevated cost of bridges, especially when compared to the cost of roads, their rational design and material selection are fundamental properties to consider when aiming to reduce the environmental impacts and lengthen the lifespan of the bridge. Especially in developing countries, the construction of new bridges (mainly short spanned) is still a necessity, and it is important that these new structures are designed according to all the sustainability parameters, instead of being based only on the construction cost. Thus, the present work aims to study short-span bridges by integrating environmental assessments into the decision-making process. To achieve this goal, three short-span bridge designs, proposed by public organizations in Brazil, are evaluated: Precast concrete bridge, mixed concrete/steel bridge, and timber bridge. In order to allow comparison, the same location and span are considered. The structures are evaluated considering the following quantitative aspects: Cost of construction, assembly and material transportation, lifespan, and environmental impact (measured by the global warming potential, GWP). In addition, some more subjective factors are considered, such as the architecture (layout and appearance) and the user¿s sensation of security. The selection is made by the adoption of two multi-criteria decision-making methods (analytic hierarchy process or AHP and Vikor). The results obtained with both methods indicate the mixed concrete/steel bridge as the most adequate alternative. Some additional analysis is performed in order to evaluate the influence of the qualitative aspects, as well as to study the importance of the variations in the costs on the results.The authors acknowledge the financial support of the Brazilian National Council for Scientific and
Technological Development (CNPq) to the first author, the financial support of the Spanish Ministry of Economy
and Competitiveness, along with FEDER funding (Project: BIA2017-85098-R) to the second author, and the support
of the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES) to the third author.Kripka, M.; Yepes, V.; Milani, CJ. (2019). Selection of Sustainable Short-Span Bridge Design in Brazil. Sustainability. 11(5):1307-01-1307-12. https://doi.org/10.3390/su11051307S1307-011307-12115Fonte, T. F. da, & Calil Júnior, C. (2007). Pontes protendidas de madeira: alternativa técnico-econômica para vias rurais. Engenharia Agrícola, 27(2), 552-559. doi:10.1590/s0100-69162007000300026Economical Short Span Concrete Bridges https://www.concreteconstruction.net/how-to/construction/economical-short-span-concrete-bridges_oVladimir, M., & Mihai, V. (2016). Economical Solutions for Short-span Bridges Using Reinforced Glue Laminated Timber and Steel. Procedia Engineering, 156, 227-232. doi:10.1016/j.proeng.2016.08.291García-Segura, T., Penadés-Plà, V., & Yepes, V. (2018). Sustainable bridge design by metamodel-assisted multi-objective optimization and decision-making under uncertainty. Journal of Cleaner Production, 202, 904-915. doi:10.1016/j.jclepro.2018.08.177Yepes, V., Martí, J. V., & García-Segura, T. (2015). Cost and CO2 emission optimization of precast–prestressed concrete U-beam road bridges by a hybrid glowworm swarm algorithm. Automation in Construction, 49, 123-134. doi:10.1016/j.autcon.2014.10.013García-Segura, T., & Yepes, V. (2016). Multiobjective optimization of post-tensioned concrete box-girder road bridges considering cost, CO2 emissions, and safety. Engineering Structures, 125, 325-336. doi:10.1016/j.engstruct.2016.07.012Ardeshir, A., Mohseni, N., Behzadian, K., & Errington, M. (2014). Selection of a Bridge Construction Site Using Fuzzy Analytical Hierarchy Process in Geographic Information System. Arabian Journal for Science and Engineering, 39(6), 4405-4420. doi:10.1007/s13369-014-1070-2García-Segura, T., Yepes, V., Martí, J. V., & Alcalá, J. (2014). Optimization of concrete I-beams using a new hybrid glowworm swarm algorithm. Latin American Journal of Solids and Structures, 11(7), 1190-1205. doi:10.1590/s1679-78252014000700007Gervásio, H., & Simões da Silva, L. (2012). A probabilistic decision-making approach for the sustainable assessment of infrastructures. Expert Systems with Applications, 39(8), 7121-7131. doi:10.1016/j.eswa.2012.01.032Penadés-Plà, V., García-Segura, T., Martí, J., & Yepes, V. (2018). An Optimization-LCA of a Prestressed Concrete Precast Bridge. Sustainability, 10(3), 685. doi:10.3390/su10030685Allah Bukhsh, Z., Stipanovic, I., Klanker, G., O’ Connor, A., & Doree, A. G. (2018). Network level bridges maintenance planning using Multi-Attribute Utility Theory. Structure and Infrastructure Engineering, 15(7), 872-885. doi:10.1080/15732479.2017.1414858Penadés-Plà, V., García-Segura, T., Martí, J., & Yepes, V. (2016). A Review of Multi-Criteria Decision-Making Methods Applied to the Sustainable Bridge Design. Sustainability, 8(12), 1295. doi:10.3390/su8121295Zavadskas, E., Antucheviciene, J., Vilutiene, T., & Adeli, H. (2017). Sustainable Decision-Making in Civil Engineering, Construction and Building Technology. Sustainability, 10(2), 14. doi:10.3390/su10010014Du, G., & Karoumi, R. (2012). Life cycle assessment framework for railway bridges: literature survey and critical issues. Structure and Infrastructure Engineering, 10(3), 277-294. doi:10.1080/15732479.2012.749289Gervásio, H., & da Silva, L. S. (2008). Comparative life-cycle analysis of steel-concrete composite bridges. Structure and Infrastructure Engineering, 4(4), 251-269. doi:10.1080/15732470600627325Hammervold, J., Reenaas, M., & Brattebø, H. (2013). Environmental Life Cycle Assessment of Bridges. Journal of Bridge Engineering, 18(2), 153-161. doi:10.1061/(asce)be.1943-5592.0000328Itoh, Y., & Kitagawa, T. (2003). Using CO2 emission quantities in bridge lifecycle analysis. Engineering Structures, 25(5), 565-577. doi:10.1016/s0141-0296(02)00167-0Saaty, T. L. (2008). Decision making with the analytic hierarchy process. International Journal of Services Sciences, 1(1), 83. doi:10.1504/ijssci.2008.017590Zamarrón-Mieza, I., Yepes, V., & Moreno-Jiménez, J. M. (2017). A systematic review of application of multi-criteria decision analysis for aging-dam management. Journal of Cleaner Production, 147, 217-230. doi:10.1016/j.jclepro.2017.01.092Manual de projeto e construção de pontes de madeira http://www.usp.br/agen/wp-content/uploads/Manual-de-Pontes-de-Madeira.pdfSantoro, J. F., & Kripka, M. (2017). Studies on Environmental Impact Assessment of Reinforced Concrete in Different Life Cycle Phases. International Journal of Structural Glass and Advanced Materials Research, 1(2), 32-40. doi:10.3844/sgamrsp.2017.32.40Zuo, J., Pullen, S., Rameezdeen, R., Bennetts, H., Wang, Y., Mao, G., … Duan, H. (2017). Green building evaluation from a life-cycle perspective in Australia: A critical review. Renewable and Sustainable Energy Reviews, 70, 358-368. doi:10.1016/j.rser.2016.11.251Mahnert, K.-C., & Hundhausen, U. (2017). A review on the protection of timber bridges. Wood Material Science & Engineering, 13(3), 152-158. doi:10.1080/17480272.2017.1403955Concrete CO2 Fact Sheet www.nrmca.org/greenconcrete/concrete%20co2%20fact%20sheet%20june%202008.pd
Synthesis of Novel Potent Dipeptidyl Peptidase IV Inhibitors with Enhanced Chemical Stability: Interplay between the N-Terminal Amino Acid Alkyl Side Chain and the Cyclopropyl Group of α-Aminoacyl-l-<i>cis</i>-4,5-methanoprolinenitrile-Based Inhibitors
No full textA series of methanoprolinenitrile-containing dipeptide mimetics were synthesized and assayed
as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV (DPP-IV). The catalytic action of DPP-IV is the principle means of degradation of glucagon-like
peptide-1, a key mediator of glucose-stimulated insulin secretion, and DPP-IV inhibition shows
clinical benefit as a novel mechanism for treatment of type 2 diabetes. However, many of the
reversible inhibitors to date suffer from chemical instability stemming from an amine to nitrile
intramolecular cyclization. Installation of a cyclopropyl moiety at either the 3,4- or 4,5-position
of traditional 2-cyanopyrrolidide proline mimetics led to compounds with potent inhibitory
activity against the enzyme. Additionally, cis-4,5-methanoprolinenitriles with β-branching in
the N-terminal amino acid provided enhanced chemical stability and high inhibitory potency.
This class of inhibitors also exhibited the ability to suppress prandial glucose elevations after
an oral glucose challenge in male Zucker rats
