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The inclusion of warm-season grasses, such as switchgrass (Panicum virgatum) and eastern gamagrass (EG) (Tripsacum dactyloides), in vegetated buffer strips has been shown to mitigate herbicide contamination in runoff and increase herbicide degradation in soil. The mode of action by which buffer strip rhizospheres enhance herbicide degradation remains unclear, but microorganisms and phytochemicals are believed to facilitate degradation processes. The objectives of this study were to: 1) screen root extracts from seven switchgrass cultivars for the ability to degrade the herbicide atrazine (ATZ) in solution; 2) determine sorption coefficients (Kd) of the ATZ-degrading phytochemical 2-ß-D-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one (DBG) to soil and Ca-montmorillonite, and investigate if DBG or ATZ sorption alters degradation processes; and 3) quantify ATZ degradation rates and soil microbial response to ATZ application in mesocosms containing soil and select warm-season grasses. Phytochemicals extracted from the roots of switchgrass cultivars degraded 44-85% of ATZ in 16-h laboratory assays, demonstrating that some switchgrass cultivars could rapidly degrade ATZ under laboratory conditions. However, attempts to isolate ATZ-degrading phytochemicals from plant roots were unsuccessful. Sorption studies revealed that DBG was strongly sorbed to soil (Kd = 87.2 L kg-1) and Ca-montmorillonite (Kd = 31.7 L kg-1), and DBG driven hydrolysis of ATZ was entirely inhibited when either ATZ or DBG were sorbed to Ca-montmorillonite. Atrazine degradation rates in mesocosm soils were rapid (t0.5 = 8.2-11.2 d), but not significantly different between soils collected from the two switchgrass cultivar mesocosms, the eastern gamagrass cultivar mesocosm, and the unvegetated mesocosm (control). Significant changes in three phospholipid fatty acid biomarkers were observed among the treatments. These changes indicated that different ATZ-degrading microbial consortia resulted in equivalent ATZ degradation rates between treatments. Results demonstrated that soil microbial response was the dominant mechanism controlling ATZ degradation in the soil studied, rather than root phytochemicals.
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Atrazina , Herbicidas , Panicum , Poluentes do Solo , Poluentes Químicos da Água , Agricultura , Atrazina/química , Bentonita , Biodegradação Ambiental , Herbicidas/química , Panicum/metabolismo , Compostos Fitoquímicos , Solo/química , Poluentes do Solo/análiseRESUMO
Row crop and livestock production contaminate soils and groundwater of the karst aquifers within south-central Kentucky's Pennyroyal Plateau. Transport of atrazine from field application to the epikarstic drainage system beneath a field with active row-crop farming was investigated. The Crumps Cave study site is a shallow autogenic drainage system with a recharge area of â¼1 ha that contains two epikarst drains (WF-1 and WF-2) which were monitored for atrazine, deethylatrazine (DEA), and deisopropylatrazine (DIA) concentrations from January 2011 to May 2012. Atrazine concentrations in both drains did not increase above winter background levels for nearly 2 mo after application when levels suddenly spiked and reached peak concentrations for the study during an event in May 2011. Atrazine, DEA, and DIA were detected in 100% of samples, and metabolites accounted for 54 to 94% of the monthly total loads, except in May 2011. Median dealkylated metabolite/atrazine ratios (DMAR) were â¼5:1 at both sites, and seasonal DMAR patterns corresponded with changes in soil temperature. These data support the hypothesis that a combination of sorption and degradation in the soil column above the epikarst controlled the transport of atrazine and its metabolites. This resulted in delayed atrazine transport after application and prolonged transport of atrazine and its weakly sorbed metabolites to the epikarst aquifer. Management practices that reduce herbicide inputs, such as diverse crop rotations, cover crops, and use of low-rate and strong-sorbing herbicides, would improve groundwater quality in areas of the Corn Belt with intensive row cropping on karst topography.
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Atrazina/análise , Monitoramento Ambiental , Herbicidas/análise , Poluentes Químicos da Água/análise , Água SubterrâneaRESUMO
We recently observed that free fatty acids impair the stimulation of glucose transport into cardiomyocytes in response to either insulin or metabolic stress. In vivo, fatty acids for the myocardium are mostly obtained from triglyceride-rich lipoproteins (chylomicrons and Very Low-Density Lipoproteins). We therefore determined whether exposure of cardiac myocytes to VLDL resulted in impaired basal and stimulated glucose transport. Primary adult rat cardiac myocytes were chronically exposed to VLDL before glucose uptake was measured in response to insulin or metabolic stress, provoked by the mitochondrial ATP synthase inhibitor oligomycin. Exposure of cardiac myocytes to VLDL reduced both insulin-and oligomycin-stimulated glucose uptake. The reduction of glucose uptake was associated with a moderately reduced tyrosine phosphorylation of the insulin receptor. No reduction of the phosphorylation of the downstream effectors of insulin signaling Akt and AS160 was however observed. Similarly only a modest reduction of the activating phosphorylation of the AMP-activated kinase (AMPK) was observed in response to oligomycin. Similar to our previous observations with free fatty acids, inhibition of fatty acid oxidation restored oligomycin-stimulated glucose uptake. In conclusions, VLDL-derived fatty acids impair stimulated glucose transport in cardiac myocytes by a mechanism that seems to be mediated by a fatty acid oxidation intermediate. Thus, in the clinical context of the metabolic syndrome high VLDL may contribute to enhancement of ischemic injury by reduction of metabolic stress-stimulated glucose uptake.
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Desoxiglucose/metabolismo , Lipoproteínas VLDL/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Transporte Biológico , Células Cultivadas , Colesterol/metabolismo , Relação Dose-Resposta a Droga , Ácidos Graxos não Esterificados/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Insulina/farmacologia , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Oligomicinas/farmacologia , Oxirredução , Fosforilação , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Receptor de Insulina/efeitos dos fármacos , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tirosina , Desacopladores/farmacologiaRESUMO
Long-term monitoring data from agricultural watersheds are needed to determine if efforts to reduce nutrient transport from crop and pasture land have been effective. Goodwater Creek Experimental Watershed (GCEW), located in northeastern Missouri, is a high-runoff-potential watershed dominated by claypan soils. The objectives of this study were to: (i) summarize dissolved NH-N, NO-N, and PO-P flow-weighted concentrations (FWC), daily loads, and yields (unit area loads) in GCEW from 1992 to 2010; (ii) assess time trends and relationships between precipitation, land use, and fertilizer inputs and nutrient transport; and (iii) provide context to the GCEW data by comparisons with other Corn Belt watersheds. Significant declines in annual and quarterly FWCs and yields occurred for all three nutrient species during the study, and the decreases were most evident for NO-N. Substantial decreases in first- and fourth-quarter NO-N FWCs and daily loads and modest decreases in first-quarter PO-P daily loads were observed. Declines in NO-N and PO-P transport were attributed to decreased winter wheat ( L.) and increased corn ( L.) production that shifted fertilizer application from fall to spring as well as to improved management, such as increased use of incorporation. Regression models and correlation analyses indicated that precipitation, land use, and fertilizer inputs were critical factors controlling transport. Within the Mississippi River Basin, NO-N yields in GCEW were much lower than in tile-drained areas, but PO-P yields were among the highest in the basin. Overall, results demonstrated that reductions in fall-applied fertilizer and improved fertilizer management reduced N and P transport in GCEW.
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Goodwater Creek Experimental Watershed (GCEW) has been the focus area of a long-term effort to document the extent of and to understand the factors controlling herbicide transport. We document the datasets generated in the 20-yr-long research effort to study the transport of herbicides to surface and groundwater in the GCEW. This long-term effort was augmented with a spatially broad effort within the Central Mississippi River Basin encompassing 12 related claypan watersheds in the Salt River Basin, two cave streams on the fringe of the Central Claypan Areas in the Bonne Femme watershed, and 95 streams in northern Missouri and southern Iowa. Details of the analytical methods, periods of record, number of samples, study locations, and means of accessing these data are provided. In addition, a brief overview of significant findings is presented. A key finding was that near-surface restrictive soil layers, such as argillic horizons of smectitic mineralogy, result in greater herbicide transport than soils with high percolation and low clay content. Because of this, streams in the claypan soil watersheds of northeastern Missouri have exceptionally high herbicide concentrations and relative loads compared with other areas of the Corn Belt.
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We document the 20-yr-long research effort to study the transport of N and P to surface and groundwater in Goodwater Creek Experimental Watershed. We also document related efforts in nearby claypan watersheds and watersheds with contrasting soil and hydrologic conditions across the northern Missouri-southern Iowa region. Details of the analytical methods, instrumentation, method detection limits, and quality assurance program used to generate the data are described along with a brief overview of significant findings. Nutrient concentrations in streams were in the range associated with nuisance algal growth and presumed loss of aquatic invertebrate diversity. Incorporation of fertilizers was shown to be the most effective practice for reducing nutrient transport in runoff. Despite the claypan soils, NO leaching was a major fate for fertilizer N, and significant contamination of the glacial till aquifer has occurred when long-term fertilizer and manure N inputs exceeded crop N requirements. A key finding of these studies was that field areas with the poorest crop growth were also the most vulnerable to nutrient as well as sediment and herbicide transport.
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Acute heart failure (AHF) is a frequent medical condition associated with a poor prognosis. Based on systolic blood pressure at presentation, patients with AHF can be classified into 5 clinical profiles enabling a more targeted use of standard medications including diuretics, vasodilators and inotropes. The most recent guidelines underline the importance of a rapid management and the favorable impact of heart failure programs, which reduce morbidity and mortality after an admission for AHF. New therapeutic perspectives include ultrafiltration, vasopressin and adenosine antagonists, relaxin and new inotropes such as istaroxime.
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Insuficiência Cardíaca/terapia , Doença Aguda , Adenosina/antagonistas & inibidores , Algoritmos , Cardiotônicos/uso terapêutico , Diuréticos/uso terapêutico , Quimioterapia Combinada , Etiocolanolona/análogos & derivados , Etiocolanolona/uso terapêutico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Hemodiafiltração , Humanos , Oxigenoterapia , Guias de Prática Clínica como Assunto , Prognóstico , Relaxina/uso terapêutico , Fatores de Risco , Resultado do Tratamento , Vasoconstritores/antagonistas & inibidores , Vasodilatadores/uso terapêutico , Vasopressinas/antagonistas & inibidoresRESUMO
After valve replacement, significant paravalvular leaks (PVL) may develop in up to 12.5% of the cases. Signs and symptoms include congestive heart failure and/or haemolysis and therefore may require reintervention. Redo valve surgery is considered the therapy of choice for symptomatic patients, either by valve replacement or leak repair. Considering the risk of morbidity and mortality associated with a surgical reintervention and the high post-surgical recurrence of PVL, the endovascular treatment represents an attractive alternative to surgery for high risk patients. The percutaneous approach aims at PVL reduction by implantation of certain occluder devices. The procedure is technically feasible in 60 to 90% of the cases according to different series. Technical success is associated with clinical improvement in 50 to 80% of the cases.
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Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/prevenção & controle , Insuficiência Cardíaca/etiologia , Hemólise , Humanos , Valva Mitral/patologia , Valva Mitral/cirurgia , Falha de Prótese , Reoperação/estatística & dados numéricosRESUMO
Streams in the Salt River Basin (SRB) of northeastern Missouri, USA, have been chronically contaminated by atrazine and metabolites, with peak annual transport occurring from spring to early summer. Since 2005, increased fall-applied simazine has introduced a second chloro-triazine herbicide that degrades to deisopropylatrazine (DIA), creating the need for a method to partition DIA between its two parent sources - i.e., DIA derived from atrazine (DIAATR) and that from simazine (DIASIM). Distinguishing DIA parent sources would extend current understanding of chloro-triazine transport, leading to more accurate risk assessments and improved watershed-scale load estimates. The objectives of this study were to evaluate proposed methods for DIA partitioning, and to apply the most effective method to estimate DIAATR and DIASIM concentrations and loads. Three DIA partition methods were developed and statistically evaluated: 1) edge-of-field (EOF) based on DIA and deethylatrazine (DEA) concentrations in runoff from atrazine treated fields; 2) DIA:DEA concentration ratios (D2R) in runoff from atrazine treated fields; and 3) concentration ratios of simazine:atrazine (SAR) in streams. Stream samples were collected year-round at 7 SRB stream sites from 2005 to 2010 and daily, quarterly, and annual concentrations and loads of atrazine, DEA, DIA, and simazine computed. The SAR method was superior to EOF and D2R in its ability to estimate concentrations and loads of DIASIM and DIAATR that were more accurate and highly correlated to observed transport of simazine, atrazine, and DIA. The SAR method results demonstrated the differences in DIASIM and DIAATR transport timing, with peak DIASIM transport occurring from mid-Nov to Apr and peak DIAATR transport from May to Jun. Dual season triazine applications within a watershed substantially increased the period of high chloro-triazine concentrations in streams from ~3 to ~8â¯months/yr, potentially increasing the risk of toxicity to aquatic ecosystems.
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A sound multi-species vegetation buffer design should incorporate the species that facilitate rapid degradation and sequestration of deposited herbicides in the buffer. A field lysimeter study with six different ground covers (bare ground, orchardgrass, tall fescue, timothy, smooth bromegrass, and switchgrass) was established to assess the bioremediation capacity of five forage species to enhance atrazine (ATR) dissipation in the environment via plant uptake and degradation and detoxification in the rhizosphere. Results suggested that the majority of the applied ATR remained in the soil and only a relatively small fraction of herbicide leached to leachates (<15%) or was taken up by plants (<4%). Biological degradation or chemical hydroxylation of soil ATR was enhanced by 20 to 45% in forage treatment compared with the control. Of the ATR residues remaining in soil, switchgrass degraded more than 80% to less toxic metabolites, with 47% of these residues converted to the less mobile hydroxylated metabolites 25 d after application. The strong correlation between the degradation of N-dealkylated ATR metabolites and the increased microbial biomass carbon in forage treatments suggested that enhanced biological degradation in the rhizosphere was facilitated by the forages. Hydroxylated ATR degradation products were the predominant ATR metabolites in the tissues of switchgrass and tall fescue. In contrast, the N-dealkylated metabolites were the major degradation products found in the other cool-season species. The difference in metabolite patterns between the warm- and cool-season species demonstrated their contrasting detoxification mechanisms, which also related to their tolerance to ATR exposure. Based on this study, switchgrass is recommended for use in riparian buffers designed to reduce ATR toxicity and mobility due to its high tolerance and strong degradation capacity.
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Atrazina/metabolismo , Herbicidas/metabolismo , Poaceae/metabolismo , Poluentes do Solo/metabolismo , Atrazina/análise , Atrazina/toxicidade , Biodegradação Ambiental , Herbicidas/análise , Herbicidas/toxicidade , Hidroxilação , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Transpiração Vegetal , Poaceae/efeitos dos fármacos , Poaceae/crescimento & desenvolvimento , Microbiologia do Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidadeRESUMO
Isoxaflutole (IXF; Balance) belongs to a new class of isoxazole herbicides. Isoxaflutole has a very short half-life in soil and rapidly degrades to a stable and phytotoxic degradate, diketonitrile (DKN). DKN was previously discovered to rapidly react with hypochlorite (OCl-) in tap water, yielding the benzoic acid (BA) degradate as a major product, but the complete reaction pathway and mechanism have not been elucidated. Thus, the objectives of this work were to (1) determine the stoichiometry of the reaction between DKN and OCl-; (2) identify products in addition to BA; and (3) propose a complete pathway and reaction mechanism for oxidation of DKN by OCl-. Stoichiometry of the reaction showed a molar ratio of OCl-/DKN of 2. In addition, two previously uncharacterized chlorinated intermediates were identified under conditions in which OCl- was the limiting reactant. The proposed chemical structure of a chlorinated benzoyl intermediate was inferred from a series of HPLC/MS and HPLC/MS/MS experiments and the use of mass spectral simulation software. A chlorinated ketone intermediate was also identified using ion trap GC/MS. Two additional end products were also identified: cyclopropanecarboxylic acid (CPCA) and dichloroacetonitrile (DCAN). On the basis of the reaction stoichiometry, the structure of the chlorinated intermediates, and the identification of the products, two reaction pathways are proposed. Both pathways involve a two-step nucleophilic attack and oxidation of the diketone structure of DKN, leading to formation of BA, DCAN, and CPCA.
Assuntos
Herbicidas/química , Ácido Hipocloroso/química , Isoxazóis/química , Nitrilas/química , Sulfonas/química , Água/química , Cromatografia Gasosa-Espectrometria de Massas , Oxirredução , Poluição da ÁguaRESUMO
A robust multi-residue procedure is needed for the analysis of the pro-herbicide isoxaflutole and its degradates in soil and plant materials at environmentally relevant (<1 microg kg-1) levels. An analytical method using turbo-spray and heat-nebulizer high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for the analysis of isoxaflutole (IXF) and its two metabolites, diketonitrile (DKN) and the benzoic acid metabolite (BA), at sub-microgram per kilogram levels in soil and plant samples. The average recoveries of the three compounds in spiked soil and plant samples ranged from 84 to 110% and 94 to 105%, respectively. The limits of quantification were validated at 0.06 microg kg-1 for soil and 0.3 microg kg-1 for plant samples. The limits of detection (LOD) for soil analysis were 0.01, 0.002, and 0.01 microg kg-1 for IXF, DKN, and BA, respectively. Corresponding LOD for the plant analysis method were 0.05, 0.01, and 0.05 microg kg-1. The developed method was validated using forage grass and soil samples collected from a field lysimeter study in which IXF was applied to each of four forage treatments. Forage plants and soils were sampled for analyses 25 days after IXF application to the soil. In soils, IXF was not detected in any treatment, and DKN was the predominant metabolite found. In forage plants, the concentrations of DKN and BA were 10-100-fold higher than that in soil samples, but IXF was not detected in any forage plants. The much higher proportion of BA to DKN in plant tissues (23-53%), as compared to soils (0-5%), suggested that these forages were capable of detoxifying DKN. The developed methods provided LODs at sub-microgram per kilogram levels to determine the fate of IXF and its metabolites in soils and forage plants, and they also represent considerable improvements in extraction recovery rates and detection sensitivity as compared to previous analytical methods for these compounds.
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Cromatografia Líquida de Alta Pressão/métodos , Herbicidas/análise , Isoxazóis/análise , Poaceae/química , Solo/análise , Espectrometria de Massas em Tandem/métodos , Ração Animal/análise , Isoxazóis/metabolismoRESUMO
Intracardiac masses of the mitral valve are rare. Their differential diagnosis is wide, ranging from tumors (myxomas, lipomas and fibroelastomas), thrombi and abnormal muscular or fibrous bands. We report a case and management. A 68 year-old asymptomatic female who had undergone coronary angioplasty and stent placement in the left anterior descending artery for acute myocardial infarction four years earlier, was shown to have, on routine follow-up, an intracardiac mass originating from the anterior leaflet of the mitral valve and prolapsing into the left ventricular outflow tract (LVOT). The patient underwent surgical excision of the mass under cardiopulmonary bypass, to prevent cerebral or coronary embolization and sudden death due to the highly sensitive location of the mass, in the high-velocity flow LVOT. A transverse aortotomy provided exposure of the ventricular surface of the anterior mitral leaflet and revealed a fusiform mass attached to the medial segment of the anterior leaflet, resembling a secondary cordae, measuring 20 by 3 mm. The implantation was calcified on the ventricular aspect of the anterior mitral leaflet. This mass was completely excised. Postoperative recovery was uneventful. Peroperative and postoperative transesophageal echocardiography were normal. Histological examination showed a partially necrosed and calcified fibrous tissue lined by endothelium. The final diagnosis was that of a mitral tendon. Intracardiac masses of the mitral valve are rare lesions, mostly papillary fibroelastomas and myxomas and more rarely mitral tendons, which require surgical resection for prevention of embolization. The definitive diagnosis is often only obtained on histological analysis.
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Neoplasias Cardíacas/cirurgia , Prolapso da Valva Mitral/cirurgia , Obstrução do Fluxo Ventricular Externo/cirurgia , Idoso , Diagnóstico Diferencial , Ecocardiografia Transesofagiana , Feminino , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/diagnóstico , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/etiologiaRESUMO
The Canadian Immunization Guide (CIG) is a trusted, reader-friendly summary of information and advice on immunization that has been used by health care providers and policy makers for decades. It is continuously updated based on new recommendations from the National Advisory Committee on Immunization (NACI) and the Committee to Advise on Tropical Medicine and Travel (CATMAT), two external advisory bodies to the Public Health Agency of Canada. In September 2016, the CIG moved to a new web platform that has improved navigability and is more mobile friendly. Between April 2015 and October 2016, five new NACI statements were published and are reflected in the CIG. The objective of this article is to provide readers with highlights of recent key changes to active vaccine recommendations in the CIG. For example, for Hepatitis (HA) vaccine, it may now be administered to persons six months of age and older and considered for all individuals receiving repeated replacement of plasma-derived clotting factors. There are now new recommendations for the use of HA immunoglobulin post-exposure prophylaxis. For Human papillomavirus (HPV) vaccine, any of the authorized HPV vaccines in Canada, including HPV9 vaccine, can be used according to the recommended HPV immunization schedules. For influenza vaccine, adults with neurologic or neurodevelopment conditions have been added to the group for whom influenza vaccination is particularly recommended, high-dose influenza vaccine has been approved for use in Canada in adults ≥65 years of age and live attenuated influenza vaccine (LAIV) is no longer a preferentially recommended product for use in children and adolescents. On an individual basis, pneumococcal conjugate 13-valent (PNEU-C-13) vaccine may be recommended to immunocompetent adults aged 65 years and older if not previously immunized against pneumococcal disease. When it is given, it should precede the pneumococcal polysaccharide 23-valent (PNEU-P-23) vaccine. Varicella immune globulin may now be administered up to 10 days since last exposure for the purpose of disease attenuation and there were a number of minor changes to the criteria for assessing varicella immunity.
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The National Advisory Committee on Immunization (NACI) provides expert and evidence-based advice to the Public Health Agency of Canada (PHAC) on the use of human vaccines in Canada. This advice is presented in a variety of publications for different uses. A recent survey identified some confusion regarding the various NACI publication products. The objective of this article is to identify the level of detail and appropriate uses of the different NACI products. NACI statements provide a synthesis of current evidence and expert opinion on new vaccines or new indications for vaccines to inform immunization practices, policies and programs. NACI literature reviews inform new NACI statements and are published after the statement to inform readers about current literature on a specific immunization topic. The Canadian Immunization Guide (CIG) is a practice-oriented guide that synthesizes all the NACI statements and is updated regularly. NACI statement summaries are published in the Canada Communicable Disease Report (CCDR) and provide a high level overview of these statements shortly after they are published. These products provide a variety of options for users to choose how in-depth they wish to explore the evidence base and process for producing recommendations for immunization in Canada.
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The role of benzoxazinones (Bx, 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one) in triazine resistance in plants has been studied for over half a century. In this research, fundamental parameters of the reaction between DIBOA-Glc (2-ß-d-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one) and atrazine (ATR, 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine) were examined. Through a series of experiments employing a variety of chromatographic and spectroscopic techniques, the DIBOA-Glc/ATR reaction was characterized in terms of reactant and product kinetics, stoichiometry, identification of a reaction intermediate, and reaction products formed. Results of these experiments demonstrated that the reaction mechanism proceeds via nucleophilic attack of the hydroxamic acid moiety of DIBOA-Glc at the C-2 position of the triazine ring to form hydroxyatrazine (HA, 2-hydroxy-4-ethylamino-6-isopropylamino-s-triazine), with associated degradation of DIBOA-Glc. Degradation of reactants followed first-order kinetics with a noncatalytic role of DIBOA-Glc. A reaction intermediate was identified as a DIBOA-Glc-HA conjugate, indicating a 1:1 DIBOA-Glc:ATR stoichiometry. Reaction products included HA and Cl(-), but definitive identification of DIBOA-Glc reaction product(s) was not attained. With these reaction parameters elucidated, DIBOA-Glc can be evaluated in terms of its potential for a myriad of applications, including its use to address the problem of widespread ATR contamination of soil and water resources.
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Benzoxazinas/química , Herbicidas/química , Triazinas/química , Estrutura MolecularRESUMO
Dicarboxylic amino acids constitute the most numerous residues of insoluble elastin in which are potentially ionizable in the physiological range of pH. These residues are essential in facilitating productive electrostatic interaction between elastase and elastin. The present study has investigated the possibility that the glutamic and aspartic acid residues of elastin are amidated. Acid-labile amide-bound ammonia of elastin was quantitated after hydrolysis of the insoluble protein with 2 M HC1 by incubating aliquots of microdistilled hydrolysates with glutamate dehydrogenase, excess alpha-ketoglutarate, and reduced nicotinamide adenine dinucleotide and measuring the resultant decrease in A340 due to oxidation of the dinucleotide cofactor. It was found that ligament elastin purified by repeated autoclaving contains approximately 2.29 mumol of acid-labile amide nitrogen per 10 mg of protein, a value equivalent to approximately 70% of the total number of dicarboxylic amino acid residues. Independent analysis of the amide content was obtained by amino acid analysis of an esterified and reduced elastin sample in which the free dicarboxylic amino acid residues had been converted to the corresponding alcohol derivatives. This analysis indicated that autoclaved ligament elastin contains approximately 18 glutamine, 3 asparagine, 4 glutamic acid and 5 aspartic acid residues per 1000 residues, in good agreement with the analysis of total acid-labile ammonia. The esterified and reduced elastin derivative was nearly inert as an elastase substrate, consistent with a lack of free dicarboxylic amino acid residues. However, addition of sodium dodecyl sulfate to this elastin derivative restores enzyme-substrate charge complementarity, and the elastin-ligand complex was readily hydrolyzed by elastase at the fully stimulated rate, emphasizing the control such ligands can exert in elastolysis. The amide bonds of elastin were found to be significantly more resistant to hydrolysis by 0.1 M NaOH at 98 degrees C than were those of lysozyme or free amidated amino acids. The finding that most of dicarboxylic amino acid residues of elastin exist at neutral amides further emphasizes the apolar character of elastin and has bearing upon the metabolic susceptibility, ligand-binding ability and structural aspects of this connective tissue protein.
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Elastina , Amidas/análise , Aminoácidos/análise , Animais , Aorta , Boroidretos , Bovinos , Fenômenos Químicos , Química , Ésteres , LigamentosRESUMO
Recent advances in molecular genetics have resulted in the identification of pathogenic mutations in a number of genes which cause hypertrophic cardiomyopathy (HCM). In order to integrate this increasing genetic knowledge of HCM into the cardiology clinic, we offer all patients and their families diagnosis and genetic counselling based on these current data. In addition, within the framework of a multidisciplinary project between the Divisions of Medical Genetics, Cardiology and Pediatric Cardiology of the University Hospitals of Geneva, we have developed a resequencing array enabling rapid molecular diagnosis of HCM. Data from this study will enhance our understanding of the aetiology of HCM, and improve our knowledge of genotype-phenotype correlations. This information will enable us to develop new therapeutic and preventive concepts, with the aim of tailoring therapies to the specific genetic variant of each patient and its family.
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Cardiomiopatia Hipertrófica/genética , Aconselhamento Genético , Testes Genéticos , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/terapia , Diagnóstico Diferencial , Predisposição Genética para Doença , Humanos , Biologia Molecular/tendênciasRESUMO
OBJECTIVES: Increasing evidence suggests that left ventricular remodeling is associated with a shift from fatty acid to glucose metabolism for energy production. The aim of this study was to determine whether left ventricular remodeling with and without late-onset heart failure after myocardial infarction is associated with regional changes in the expression of regulatory proteins of glucose or fatty acid metabolism. METHODS: Myocardial infarction was induced in rats by ligation of the left anterior descending coronary artery (LAD). In infarcted and sham-operated hearts the peri-infarction region (5-mm zone surrounding the region at risk), the interventricular septum and the right ventricular free wall were separated for analysis. RESULTS: At 8 and 20 weeks after LAD ligation, the peri-infarction region and the septum exhibited marked re-expression of atrial natriuretic factor [+252+/-37 and +1093+/-279%, respectively, in the septum (P<0.05)] and of alpha-smooth muscle actin [+34+/-10 and +43+/-14%, respectively, in the septum (P<0.05)]. At 8 weeks, when left ventricular hypertrophy was present without signs of heart failure, myocardial mRNA expression of glucose transporters (GLUT-1 and GLUT-4) was not altered, whereas mRNA expression of medium-chain acyl-CoA dehydrogenase (MCAD) was significantly reduced in the peri-infarction region (-25+/-7%; P<0.05). In hearts exhibiting heart failure 20 weeks after infarct-induction there was a change in all three ventricular regions of both mRNA and protein content of GLUT-1 [+72+/-28 and +121+/-15%, respectively, in the peri-infarction region (P<0.05)] and MCAD [-29+/-9 and -56+/-4%, respectively, in the peri-infarction region (P<0.05)]. CONCLUSION: In rats with large myocardial infarction, progression from compensated remodeling to overt heart failure is associated with upregulation of GLUT-1 and downregulation of MCAD in both the peri-infarction region and the septum.
Assuntos
Metabolismo Energético , Ácidos Graxos/metabolismo , Insuficiência Cardíaca/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas Musculares , Infarto do Miocárdio/metabolismo , Acil-CoA Desidrogenases/metabolismo , Animais , Biomarcadores/análise , Northern Blotting/métodos , Western Blotting/métodos , Ácidos Graxos/genética , Regulação da Expressão Gênica , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 4 , Insuficiência Cardíaca/diagnóstico , Modelos Animais , Ratos , Ratos Endogâmicos , Fatores de Tempo , Remodelação VentricularRESUMO
To delineate beneficial effects of intracoronary thrombolysis on myocardial metabolism in vivo and their dependence on the interval after coronary occlusion prior to reperfusion, we studied 23 closed-chest dogs. Coronary occlusion was produced with a thrombogenic copper coil to performance of cardiac positron emission tomography with 11C-palmitate. Jeopardized zones were calculated by summation by myocardial regions exhibiting less than 50 percent of the peak left ventricular wall radioactivity, and residual metabolic activity within jeopardized zones quantified based on the average counts compared with average counts in normal myocardium. After tomography, streptokinase was infused into the coronary artery (4,000 units per minute), resulting in angiographically demonstrable restoration of patency. Repeat tomography performed 90 minutes after the initial study with a second injection of 11C-palmitate demonstrated reduction of jeopardized zones by 51 +/- 6.3 percent (SE) and by 21 +/- 1.8 (p less than 0.01 based on paired comparisons) when refusion was initiated 1 to 2 (in four dogs) or 2 to 4 (in six dogs) hours after occlusion. Metabolic activity in initially jeopardized regions increased by 111 +/- 24.3 percent and 61.8 +/- 12.6 (p less than 0.01 for each). When streptokinase was infused later after occlusion, significant salutary metabolic effects did not occur. These results indicate that positron tomography may be useful in the clinical delineation of the efficacy of thrombolytic therapy in restoring myocardial metabolism and underscore the marked dependence of such efficacy on the duration of the interval of ischemia prior to the onset of reperfusion.