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1.
World J Hepatol ; 16(6): 883-890, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38948435

RESUMO

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient's survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

2.
Sci Rep ; 14(1): 3892, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365927

RESUMO

Several RF and microwave radiating devices, such as horn antennas, Fabry-Perot cavity antennas, and aperture-fed focusing devices, are excited through rectangular waveguides. The impedance matching of the overall system (from the waveguide feed to the radiating aperture) is a task of crucial importance that is often addressed by means of brute-force parameter-sweep full-wave analyses or blind optimization algorithms. In both cases, a significant amount of memory and time resources are required. For this purpose, we propose here a simple, yet effective solution, which only requires a single full-wave simulation and a semi-analytical procedure. The former is used to retrieve the antenna input impedance at the end of the waveguide port excitation. The semi-analytical procedure consists in a transmission-line equivalent circuit that models two waveguide discontinuities (namely two capacitive irises) within the waveguide section, whose position and geometric features are finely tuned to obtain a satisfactory impedance matching around the working frequency. The proposed method is shown to be effective in diverse and attractive application-oriented contexts, from the impedance matching of a Fabry-Perot cavity antenna to that of a wireless near-field link between two aperture-fed focusing devices. A remarkable agreement between full-wave simulations and numerical results is found in all cases. Thanks to its versatility, simplicity, and a rather low demand of computational resources, the proposed approach may become an essential tool for the effective design of waveguide-fed antennas.

3.
Nat Food ; 4(9): 810-822, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37709937

RESUMO

The European Union (EU) plans to decarbonize the region by 2050. As highlighted by the Green Deal and Farm to Fork Strategy, food systems are essential for this transition. Here we investigate the resource dependence and carbon emissions of the EU-27's food systems from 2004 to 2014 via an ecological footprint (EF)-extended multi-regional input-output approach, accounting for demand and supply (including trade), and considering multiple externalities. Food contributes towards almost a third of the region's EF, and appropriates over half of its biocapacity. Average reliance on biocapacity within national borders decreased, while reliance on intra-EU biocapacity increased; yet a quarter of the biocapacity for food consumption originates from non-EU countries. Despite a reduction in both total EF and food EF over the study period, EU-27 residents demand more from nature than the region's ecosystems can regenerate-highlighting the need for new or strengthened food and trade policies to enable a transformation to sustainable EU food systems.


Assuntos
Carbono , Ecossistema , União Europeia , Fazendas , Alimentos
4.
Clin Transplant ; 37(10): e15057, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37350743

RESUMO

BACKGROUND: The post-operative course after Liver Transplantation (LT) can be complicated by early allograft dysfunction (EAD), primary nonfunction (PNF) and death. A lactate concentration at the end of transplant of ≥5 mmol/L was recently proposed as a predictive marker of PNF, EAD, and mortality; this study aimed to validate these previous reports in a large single center cohort. METHODS: This retrospective cohort study included adult liver transplant recipients who received grafts from deceased donors at our center between June 2012 and May 2021. Receiver operating characteristic (ROC) curves for the lactate concentration at the end of transplantation were computed to determine the AUC for PNF, EAD and mortality at 90 days. RESULTS: In our cohort of 1137 cases, the AUCs for lactate to predict EAD, PNF and mortality were respectively .56 (95% confidence interval [CI]: .53-.60), .69 (95% CI: .52-.85), and .74 (95% CI: .63-.84). CONCLUSION: The clinical value of lactate concentration at the end of transplantation to predict PNF, EAD and mortality at 90 days was, at best, modest, as shown by the relatively low AUCs. Our findings cannot validate previous reports that the lactate level alone is a good predictor of poor outcomes after liver transplantation.


Assuntos
Transplante de Fígado , Disfunção Primária do Enxerto , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Ácido Láctico , Estudos Retrospectivos , Sobrevivência de Enxerto , Transplante Homólogo , Aloenxertos , Disfunção Primária do Enxerto/etiologia , Fatores de Risco
5.
Sci Total Environ ; 886: 163960, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37149183

RESUMO

Chicken meat production in the European Union (EU) causes environmental pressures within and beyond the EU, mostly due to feed consumption. The expected dietary shift from red to poultry meat will drive changes in the demand for chicken feeds and the associated environmental impacts, calling for a renewed attention on this supply chain. By performing a break-down analysis based on material flow accounting, this paper assesses the annual environmental burden caused within and outside of the EU by each single feed consumed by the EU chicken meat industry from 2007 to 2018. The increased feed demand required to support the growth of the EU chicken meat industry over the analyzed period caused a 17 % increase in cropland use - 6.7 million hectares in 2018. Instead, CO2 emissions linked to feed demand decreased by ~45 % over the same period. Despite an overall improvement in resource and impact intensity, chicken meat production was not decoupled from environmental burden. In 2018, 0.40 Mt. of nitrogen, 0.28 Mt. of phosphorous, and 0.28 Mt. of potassium inorganic fertilizers were implied. Our findings indicate that the sector is not yet compliant with the EU sustainability targets defined in the Farm To Fork Strategy, calling for an urgent need to fill existing policy implementation gaps. The EU chicken meat industry's environmental footprints were driven by endogenous factors such as the feed use efficiency at the chicken farming stage and the feed cultivation efficiency within the EU, as well as by exogenous factors such as the import of feed via international trade. Limitations on the use of alternative feed sources, as well as the exclusion of the imports from the EU legal framework constitute a crucial gap, which hamper fully leveraging existing solutions.


Assuntos
Galinhas , Comércio , Animais , União Europeia , Internacionalidade , Carne/análise
6.
Clin Transplant ; 37(1): e14854, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36380529

RESUMO

INTRODUCTION: In 2013, a new liver transplant allocation policy (Share 35) aimed to reduce waitlist-mortality was introduced in the United States. Regional organ sharing for recipients with a MELD score of ≥35 was prioritized over local allocation to those with lower MELD scores. Our aim was to assess the changes in perioperative mortality following the introduction of Share 35 as well as changes in patients' short-term 7-day survival, patients discharged alive and 1-year survival. Analyses were also carried out for the subgroups of patients with MELD scores ≥ and < 35. METHODS: We used data from the Scientific Registry of Transplant Recipients and included liver transplants between March 2002 and December 2018 in this retrospective cohort study. Perioperative mortality was defined as death during and within two days of liver transplant. We used robust interrupted time series analyses to evaluate the impact of Share 35 on mortality. RESULTS: We included 90 002 liver transplants in our analysis and observed a decreasing trend in perioperative mortality over time (-.061 deaths per 1000 cases per month, 95% CI -.084 to -.037, p < .001). Share 35 was not associated with a change in perioperative mortality (p = .33), short-term 7-day survival (p = .48), survival to discharge (p = .56), or 1-year survival (p = .27). CONCLUSIONS: Prioritizing sicker recipients with a MELD score ≥35 for liver transplantation was not associated with a change in postoperative mortality.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Estados Unidos/epidemiologia , Doença Hepática Terminal/cirurgia , Estudos Retrospectivos , Políticas , Listas de Espera , Índice de Gravidade de Doença
7.
Micromachines (Basel) ; 13(12)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36557529

RESUMO

Resonant Bessel-beam launchers are low-cost, planar, miniaturized devices capable of focusing electromagnetic radiation in a very efficient way in various frequency ranges, with recent increasing interest for microwave and millimeter-wave applications (i.e., 3-300 GHz). In recent years, various kinds of launchers have appeared, with different feeding mechanisms (e.g., coaxial probes, resonant slots, or loop antennas), field polarization (radial, azimuthal, and longitudinal), and manufacturing technology (axicon lenses, radial waveguides, or diffraction gratings). In this paper, we review the various features of these launchers both from a general electromagnetic background and a more specific leaky-wave interpretation. The latter allows for deriving a useful set of design rules that we here show to be applicable to any type of launcher, regardless its specific realization. Practical examples are discussed, showing a typical application of the proposed design workflow, along with a possible use of the launchers in a modern context, such as that of wireless power transfer at 90 GHz.

8.
Reg Environ Change ; 21(2): 33, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776560

RESUMO

Wetlands are critically important for biodiversity and human wellbeing, but face a range of challenges. This is especially true in the Mediterranean region, where wetlands support endemic and threatened species and remain integral to human societies, but have been severely degraded in recent decades. Here, in order to raise awareness of future challenges and opportunities for Mediterranean wetlands, and to inform proactive research and management, we identified (a) 50 key issues that might affect Mediterranean wetlands between 2020 and 2050, and (b) 50 important research questions that, if answered, would have the greatest impact on the conservation of Mediterranean wetlands between 2020 and 2050. We gathered ideas through an online survey and review of recent literature. A diverse assessment panel prioritised ideas through an iterative, anonymised, Delphi-like process of scoring, voting and discussion. The prioritised issues included some that are already well known but likely to have a large impact on Mediterranean wetlands in the next 30 years (e.g. the accumulation of dams and reservoirs, plastic pollution and weak governance), and some that are currently overlooked in the context of Mediterranean wetlands (e.g. increasing desalination capacity and development of antimicrobial resistance). Questions largely focused on how best to carry out conservation interventions, or understanding the impacts of threats to inform conservation decision-making. This analysis will support research, policy and practice related to environmental conservation and sustainable development in the Mediterranean, and provides a model for similar analyses elsewhere in the world. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10113-020-01743-1.

9.
Sci Total Environ ; 749: 141307, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-32846345

RESUMO

The food system is increasingly acknowledged as the single largest reason for humans' transgression of key planetary limits and it is gaining centrality in our societal run-up towards a sustainable future, especially at city level. In Portugal, a country characterized by high meat and fish consumption, noticeable food wastage, and high urbanization level, fully understanding and then transforming the food system is of priority. Here we investigate the significance of food in comparison to other daily anthropogenic demands and the current sourcing and resource intensities profiles of dietary patterns at Portuguese national and city level through Ecological Footprint Accounting. A critical assessment of gaps in national and local food policies to trigger a major transformation in the Portuguese food system is also conducted on the basis of a newly proposed analytical framework. Results show that food consumption in Portugal is the single largest reason (≈30%) for transgressing the carrying capacity of Earth ecosystems but, despite the urgent need for changes in Portuguese food systems, major deficiencies in local policy implementation exist with weak policy commitment, coordination, and lacking institutional capacity as food policies - especially at the local level - are still not prioritized. Similarities with other countries within Europe and their implications are also discussed.

10.
J Clin Med ; 8(11)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717387

RESUMO

Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery (DO2), the aim of this study was to investigate the effectiveness and safety of different DO2, using human red blood cells (RBCs) as oxygen carriers on metabolic recovery in a rat model of NMP. Four experimental groups (n = 5 each) consisted of (1) native (untreated/control), (2) liver static cold storage (SCS) 30 min without NMP, (3) SCS followed by 120 min of NMP with Dulbecco-Modified-Eagle-Medium as perfusate (DMEM), and (4) similar to group 3, but perfusion fluid was added with human RBCs (hematocrit 15%) (BLOOD). Compared to DMEM, the BLOOD group showed increased liver DO2 (p = 0.008) and oxygen consumption ( V O ˙ 2) (p < 0.001); lactate clearance (p < 0.001), potassium (p < 0.001), and glucose (p = 0.029) uptake were enhanced. ATP levels were likewise higher in BLOOD relative to DMEM (p = 0.031). V O ˙ 2 and DO2 were highly correlated (p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO2 and V O ˙ 2. No human RBC related damage was detected. In conclusion, an optimized DO2 significantly reduces hypoxic damage-related effects occurring during NMP. Human RBCs can be safely used as oxygen carriers.

11.
Sci Total Environ ; 693: 133642, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31635013

RESUMO

The number of publications on environmental footprint indicators has been growing rapidly, but with limited efforts to integrate different footprints into a coherent framework. Such integration is important for comprehensive understanding of environmental issues, policy formulation and assessment of trade-offs between different environmental concerns. Here, we systematize published footprint studies and define a family of footprints that can be used for the assessment of environmental sustainability. We identify overlaps between different footprints and analyse how they relate to the nine planetary boundaries and visualize the crucial information they provide for local and planetary sustainability. In addition, we assess how the footprint family delivers on measuring progress towards Sustainable Development Goals (SDGs), considering its ability to quantify environmental pressures along the supply chain and relating them to the water-energy-food-ecosystem (WEFE) nexus and ecosystem services. We argue that the footprint family is a flexible framework where particular members can be included or excluded according to the context or area of concern. Our paper is based upon a recent workshop bringing together global leading experts on existing environmental footprint indicators.

12.
Sci Rep ; 8(1): 17741, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30532010

RESUMO

A low-cost compact planar leaky-wave antenna (LWA) is proposed offering directive broadside radiation over a significantly wide bandwidth. The design is based on an annular metallic strip grating (MSG) configuration, placed on top of a dual-layer grounded dielectric substrate. This defines a new two-layer parallel-plate open waveguide, whose operational principles are accurately investigated. To assist in our antenna design, a method-of-moments dispersion analysis has been developed to characterize the relevant TM and TE modes of the perturbed guiding structure. By proper selection of the MSG for a fabricated prototype and its supporting dielectric layers as well as the practical TM antenna feed embedded in the bottom ground plane, far-field pencil-beam patterns are observed at broadside and over a wide frequency range, i.e., from 21.9 GHz to 23.9 GHz, defining a radiating percentage bandwidth of more than 8.5%. This can be explained by a dominantly excited TM mode, with low dispersion, employed to generate a two-sided far-field beam pattern which combines to produce a single beam at broadside over frequency. Some applications of this planar antenna include radar and satellite communications at microwave and millimeter-wave frequencies as well as future 5G communication devices and wireless power transmission systems.

13.
Eur J Intern Med ; 53: 52-56, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29559199

RESUMO

BACKGROUND: According to guidelines, single determination of B-type Natriuretic peptide (BNP) should be used for distinguishing between cardiac and non-cardiac acute dyspnea at the emergency room. BNP measurement is also recommended before hospital discharge in patients hospitalized for heart failure to assess prognosis and to evaluate treatment efficacy. In acute cardiogenic pulmonary edema, BNP is measured using a single BNP determination, but the temporal behavior of BNP during pulmonary edema recovery is unknown. METHODS: Fifty chronic low ejection fraction (<40%) heart failure patients (age 77 ±â€¯9 years, 17 M-33F) admitted for acute pulmonary edema were studied. Patients were grouped according to 50% dyspnea recovery time into 3 groups: ≤30 min (n = 14), 30 to 60 min (n = 19), and > 60 min (n = 17). BNP was measured at arrival and 4, 8, 12 and 24 h afterwards. RESULTS: At arrival, BNP was elevated in all patients without significant difference among groups. In the entire population, BNP median and interquartile range value were 791 (528-1327) pg/ml, 785(559-1299) pg/ml, 1014(761-1573) pg/ml, 1049(784-1412) pg/ml, 805(497-1271) pg/ml at arrival and 4, 8, 12 and 24 h afterwards, respectively, showing higher values at 8 and 12 h. This peculiar temporal behavior of BNP was shared by all study groups. Patients with the longest edema resolution showed the highest BNP level 8 and 12 h after admission. CONCLUSIONS: In acute pulmonary edema, BNP increased up to 12 h after emergency admission regardless of dyspnea recovery time, making BNP quantitative meaning in the acute phase of pulmonary edema uncertain.


Assuntos
Dispneia/sangue , Peptídeo Natriurético Encefálico/sangue , Edema Pulmonar/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Dispneia/complicações , Feminino , Insuficiência Cardíaca/sangue , Hospitalização , Humanos , Itália , Masculino , Prognóstico , Edema Pulmonar/complicações , Edema Pulmonar/fisiopatologia , Curva ROC , Centros de Atenção Terciária , Fatores de Tempo
14.
Front Med (Lausanne) ; 4: 203, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29214153

RESUMO

BACKGROUND: The role of cerebrospinal fluid (CSF) biomarkers, and neuroimaging in the diagnostic process of Alzheimer's disease (AD) is not clear, in particular in the older patients. OBJECTIVE: The aim of this study was to compare the clinical diagnosis of AD with CSF biomarkers and with cerebrovascular damage at neuroimaging in a cohort of geriatric patients. METHODS: Retrospective analysis of medical records of ≥65-year-old patients with cognitive impairment referred to an Italian geriatric outpatient clinic, for whom the CSF concentration of amyloid-ß (Aß), total Tau (Tau), and phosphorylated Tau (p-Tau) was available. Clinical diagnosis (no dementia, possible and probable AD) was based on the following two sets of criteria: (1) the Diagnostic Statistical Manual of Mental Disorders (DSM-IV) plus the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and (2) the National Institute on Aging-Alzheimer's Association (NIA-AA). The Fazekas visual scale was applied when a magnetic resonance imaging scan was available. RESULTS: We included 94 patients, mean age 77.7 years, mean Mini Mental State Examination score 23.9. The concordance (kappa coefficient) between the two sets of clinical criteria was 70%. The mean CSF concentration (pg/ml) (±SD) of biomarkers was as follows: Aß 687 (±318), Tau 492 (±515), and p-Tau 63 (±56). There was a trend for lower Aß and higher Tau levels from the no dementia to the probable AD group. The percentage of abnormal liquor according to the local cutoffs was still 15 and 21% in patients without AD based on the DSM-IV plus NINCDS-ADRDA or the NIA-AA criteria, respectively. The exclusion of patient in whom normotensive hydrocephalus was suspected did not change these findings. A total of 80% of patients had the neuroimaging report describing chronic cerebrovascular damage, while the Fazekas scale was positive in 45% of patients overall, in 1/2 of no dementia or possible AD patients, and in about 1/3 of probable AD patients, with no difference across ages. CONCLUSION: We confirmed the expected discrepancy between different approaches to the diagnosis of AD in a geriatric cohort of patients with cognitive impairment. Further research is needed to understand how to interpret this discrepancy and provide clinicians with practical guidelines.

15.
Sci Total Environ ; 578: 383-391, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27838057

RESUMO

Securing food for growing populations while minimizing environmental externalities is becoming a key topic in the current sustainability debate. This is particularly true in the Mediterranean region, which is characterized by scarce natural resources and increasing climate-related impacts. This paper focuses on the pressure Mediterranean people place on the Earth ecosystems because of their food consumption and sourcing patterns and then explores ways in which such pressure can be reduced. To do so, it uses an Ecological-Footprint-Extended Multi-Regional Input-Output (EF-MRIO) approach applied to 15 Mediterranean countries. Results indicate that food consumption is a substantial driver of the region's ecological deficit, whereby demand for renewable resources and ecosystems services outpaces the capacity of its ecosystems to provide them. Portugal, Malta and Greece are found to have the highest per capita food Footprints (1.50, 1.25 and 1.22 global hectares (gha), respectively), while Slovenia, Egypt and Israel have the lowest (0.63, 0.64 and 0.79gha, respectively). With the exception of France, all Mediterranean countries rely on the biocapacity of foreign countries to satisfy their residents' demand for food. By analyzing the effect of shifting to a calorie-adequate diet or changing dietary patterns, we finally point out that the region's Ecological Footprint - and therefore its ecological deficit - could be reduced by 8% to 10%.


Assuntos
Conservação dos Recursos Naturais , Abastecimento de Alimentos , Agricultura , Dieta , Egito , França , Grécia , Humanos , Israel , Malta , Região do Mediterrâneo , Portugal , Eslovênia
16.
Science ; 346(6206): 241-4, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25278504

RESUMO

In 2010, the international community, under the auspices of the Convention on Biological Diversity, agreed on 20 biodiversity-related "Aichi Targets" to be achieved within a decade. We provide a comprehensive mid-term assessment of progress toward these global targets using 55 indicator data sets. We projected indicator trends to 2020 using an adaptive statistical framework that incorporated the specific properties of individual time series. On current trajectories, results suggest that despite accelerating policy and management responses to the biodiversity crisis, the impacts of these efforts are unlikely to be reflected in improved trends in the state of biodiversity by 2020. We highlight areas of societal endeavor requiring additional efforts to achieve the Aichi Targets, and provide a baseline against which to assess future progress.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Extinção Biológica
17.
Sci Total Environ ; 461-462: 813-8, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23273807

RESUMO

Currently, the European economy is using nearly three times the ecological assets that are locally available. This situation cannot be sustained indefinitely. Tools are needed that can help reverse the unsustainable trend. In 2010, an EC funded One Planet Economy Network: Europe (OPEN:EU) project was launched to develop the evidence and innovative practical tools that will allow policy-makers and civil society to identify policy interventions to transform Europe into a One Planet Economy, by 2050. Building on the premise that no indicator alone is able to comprehensively monitor (progress towards) sustainability, the project has drawn on the Ecological, Carbon and Water Footprints to define a Footprint Family suite of indicators, to track human pressure on the planet. An environmentally-extended multi-regional input-output (MRIO) model has then been developed to group the Footprint Family under a common framework and combine the indicators in the family with national economic accounts and trade statistics. Although unable to monitor the full spectrum of human pressures, once grouped within the MRIO model, the Footprint Family is able to assess the appropriation of ecological assets, GHG emissions as well as freshwater consumption and pollution associated with consumption of specific products and services within a specified country. Using MRIO models within the context of Footprint analyses also enables the Footprint Family to take into account full production chains with technologies specific to country of origin.


Assuntos
Conservação dos Recursos Naturais/métodos , Meio Ambiente , Aquecimento Global , Internacionalidade , Modelos Econômicos , Carbono/análise , Europa (Continente) , Humanos , Qualidade da Água , Abastecimento de Água
18.
Eur J Med Chem ; 54: 470-82, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22704999

RESUMO

Based on our 3-hydroxy-7-chloroquinazoline-2,4-dione derivatives, previously reported as antagonists at ionotropic glutamate receptors, we synthesized new 3-hydroxyquinazoline-2,4-diones bearing a trifluoromethyl group at the 7-position and different groups at position 6. Glycine/NMDA, AMPA and kainate receptor binding data showed that the 7-trifluoromethyl residue increased AMPA and kainate receptor affinity and selectivity, with respect to the 7-chlorine atom. Among the probed 6-substituents, the 6-(1,2,4-triazol-4-yl) group (compound 8) was the most advantageous for AMPA receptor affinity and selectivity. Derivative 8 demonstrated to be effective in decreasing neuronal damage produced by oxygen and glucose deprivation in organotypic rat hippocampal slices and also showed anticonvulsant effects in pentylenetetrazole-induced convulsions. The previously reported kainate receptor antagonist 6-(2-carboxybenzoyl)-amino-7-chloro-3-hydroxyquinazoline-2,4-dione 3 prevented the failure of neurotransmission induced by oxygen and glucose deprivation in the CA1 region of rat hippocampal slices.


Assuntos
Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Simulação de Acoplamento Molecular , Quinazolinonas/química , Quinazolinonas/farmacologia , Receptores de AMPA/antagonistas & inibidores , Receptores de Ácido Caínico/antagonistas & inibidores , Animais , Anticonvulsivantes/síntese química , Anticonvulsivantes/metabolismo , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Glucose/deficiência , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiologia , Humanos , Técnicas In Vitro , Masculino , Camundongos , Oxigênio/metabolismo , Quinazolinonas/síntese química , Quinazolinonas/metabolismo , Ratos , Ratos Wistar , Receptores de AMPA/química , Receptores de AMPA/metabolismo , Receptores de Ácido Caínico/química , Receptores de Ácido Caínico/metabolismo , Relação Estrutura-Atividade , Especificidade por Substrato
19.
Science ; 328(5982): 1164-8, 2010 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-20430971

RESUMO

In 2002, world leaders committed, through the Convention on Biological Diversity, to achieve a significant reduction in the rate of biodiversity loss by 2010. We compiled 31 indicators to report on progress toward this target. Most indicators of the state of biodiversity (covering species' population trends, extinction risk, habitat extent and condition, and community composition) showed declines, with no significant recent reductions in rate, whereas indicators of pressures on biodiversity (including resource consumption, invasive alien species, nitrogen pollution, overexploitation, and climate change impacts) showed increases. Despite some local successes and increasing responses (including extent and biodiversity coverage of protected areas, sustainable forest management, policy responses to invasive alien species, and biodiversity-related aid), the rate of biodiversity loss does not appear to be slowing.


Assuntos
Biodiversidade , Ecossistema , Internacionalidade , Animais , Antozoários , Conservação dos Recursos Naturais/tendências , Extinção Biológica , Humanos , Cooperação Internacional , Plantas , Dinâmica Populacional , Fatores de Tempo , Árvores , Vertebrados
20.
Chem Pharm Bull (Tokyo) ; 57(8): 826-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19652407

RESUMO

Previous studies have shown that 8-chloro-5,6-dihydro-5-oxo-pyrazolo[1,5-c]quinazoline-2-carboxylates (PQZ series) represent a family of glycine/N-methyl-D-aspartic acid (NMDA) and/or (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and/or kainic acid (KA) receptor antagonists. Moreover, some groups have been identified that introduced in suitable positions of the PQZ 2-carboxylate framework shift affinity and selectivity toward glycine/NMDA receptor. These substituents are a carboxylate function at position-1 and/or a chlorine atom at position-9. In this paper we report a study on some new 5,6-dihydro-5-oxo-pyrazolo[1,5-c]quinazoline-1-carboxylates bearing at position-2 a lipophilic amide group or lacking substituent at this same position. All the newly synthesised compounds were evaluated for their binding at glycine/NMDA, AMPA and KA receptors. These studies led to the identification of some new PQZ derivatives endowed with good glycine/NMDA receptor affinity and selectivity and to better definition of the structure-activity relationship (SAR) of this class of compounds.


Assuntos
Pirazóis/síntese química , Pirazóis/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Receptores de Glicina/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Estrutura Molecular , Pirazóis/química , Quinazolinas/química , Estereoisomerismo , Relação Estrutura-Atividade
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