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Cities are wrestling with the practical challenges of transitioning urban water services to become water sensitive; capable of enhancing liveability, sustainability, resilience and productivity in the face of climate change, rapid urbanisation, degraded ecosystems and ageing infrastructure. Indicators can be valuable for guiding actions for improvement, but there is not yet an established index that measures the full suite of attributes that constitute water sensitive performance. This paper therefore presents the Water Sensitive Cities (WSC) Index, a new benchmarking and diagnostic tool to assess the water sensitivity of a municipal or metropolitan city, set aspirational targets and inform management responses to improve water sensitive practices. Its 34 indicators are organised into seven goals: ensure good water sensitive governance, increase community capital, achieve equity of essential services, improve productivity and resource efficiency, improve ecological health, ensure quality urban spaces, and promote adaptive infrastructure. The WSC Index design is a quantitative framework based on qualitative rating descriptions and a participatory assessment methodology, enabling local contextual interpretations of the indicators while maintaining a robust universal framework for city comparison and benchmarking. The paper demonstrates its application on three illustrative cases. Rapid uptake of the WSC Index in Australia highlights its value in helping stakeholders develop collective commitment and evidence-based priorities for action to accelerate their city's water sensitive transition. Early testing in cities in Asia, the Pacific and South Africa has also showed the potential of the WSC Index internationally.
Assuntos
Ecossistema , Água , Austrália , Cidades , África do SulRESUMO
Cities are wrestling with the practical challenges of transitioning urban water services to become water sensitive; capable of enhancing liveability, sustainability, resilience and productivity in the face of climate change, rapid urbanisation, degraded ecosystems and ageing infrastructure. Indicators can be valuable for guiding actions for improvement, but there is not yet an established index that measures the full suite of attributes that constitute water sensitive performance. This paper therefore presents the Water Sensitive Cities (WSC) Index, a new benchmarking and diagnostic tool to assess the water sensitivity of a municipal or metropolitan city, set aspirational targets and inform management responses to improve water sensitive practices. Its 34 indicators are organised into seven goals: ensure good water sensitive governance, increase community capital, achieve equity of essential services, improve productivity and resource efficiency, improve ecological health, ensure quality urban spaces, and promote adaptive infrastructure. The WSC Index design as a quantitative framework based on qualitative rating descriptions and a participatory assessment methodology enables local contextual interpretations of the indicators, while maintaining a robust universal framework for city comparison and benchmarking. The paper demonstrates its application on three illustrative cases. Rapid uptake of the WSC Index in Australia highlights its value in helping stakeholders develop collective commitment and evidence-based priorities for action to accelerate their city's water sensitive transition. Early testing in cities in Asia and the Pacific has also showed the potential of the WSC Index internationally.
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This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture. This article is part of the theme issue 'Urban flood resilience'.
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Long term planning of urban water infrastructure requires acknowledgement that transitions in the water system are driven by changes in the urban environment, as well as societal dynamics. Inherent to the complexity of these underlying processes is that the dynamics of a system's evolution cannot be explained by linear cause-effect relationships and cannot be predicted under narrow sets of assumptions. Planning therefore needs to consider the functional behaviour and performance of integrated flexible infrastructure systems under a wide range of future conditions. This paper presents the first step towards a new generation of integrated planning tools that take such an exploratory planning approach. The spatially explicit model, denoted DAnCE4Water, integrates urban development patterns, water infrastructure changes and the dynamics of socio-institutional changes. While the individual components of the DAnCE4Water model (i.e. modules for simulation of urban development, societal dynamics and evolution/performance of water infrastructure) have been developed elsewhere, this paper presents their integration into a single model. We explain the modelling framework of DAnCE4Water, its potential utility and its software implementation. The integrated model is validated for the case study of an urban catchment located in Melbourne, Australia.
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Planejamento de Cidades , Drenagem Sanitária , Modelos Teóricos , Reforma Urbana , Abastecimento de Água , Austrália , Software , ÁguaRESUMO
Since its discovery over thirty years ago, the role played by Nerve Growth Factor (NGF) in the development and maintenance of sympathetic and sensory neurons of the peripheral nervous system has been well established and extensively studied. In addition, the existing data suggest that NGF may offer neuroprotection to dorsal root ganglion neurons against drug- and diabetes-induced neurotoxicity. Based upon its neurotrophic and neuroprotective activities, the systemic administration of NGF has been proposed as a treatment for several types of neurodegenerative diseases including diabetic neuropathy. The cloning of the human gene and the subsequent large-scale production of recombinant human NGF (rhNGF) has allowed for the initiation of comprehensive preclinical animal studies and the initiation of human clinical trials. Results from recent preclinical studies indicated no safety findings which would preclude the chronic administration of rhNGF in clinical trials in humans. Initial Phase I clinical studies in humans indicated that rhNGF produced mild to moderate myalgias shortly following single intravenous or subcutaneous doses of 1 microgram/kg; in general, these effects were not observed at lower doses following single- or multiple-dosing. In addition, following multiple dosing some peripheral neuropathic patients reported an improvement in clinical symptoms which in some cases correlated with improvements in neurological examinations. Future blinded clinical trials should provide important data relevant to the potential therapeutic use of rhNGF.
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Fatores de Crescimento Neural/farmacologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Humanos , Recombinação GenéticaRESUMO
Reconstituted high-density lipoprotein (rHDL), an artificial lipoprotein consisting of apolipoprotein A-I and phosphatidylcholine (1:150, molar ratios) dose-dependently reduces lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF) production in in vitro, ex-vivo, and in-vivo model systems. In an in-vitro whole blood assay, rHDL (1 mg/ml) added concomitantly with LPS increased cellular resistence to LPS stimulation approximately 1000-fold. Even with extremely high levels of LPS (10 micrograms/ml), rHDL > or = 0.5 mg/ml caused > 50% decrease in TNF production. Preincubation of rHDL with LPS was not required for activity. rHDL (> or = 1 mg/ml) reduced TNF production by 50% even when added to cultures 2 hr after their stimulation with LPS (10 micrograms/ml). In an ex-vivo study, rabbits were infused with rHDL at doses of 25, 50, and 75 mg/kg. Blood was drawn and stimulated with LPS ex vivo and bioactive TNF was assessed using the L929 cytotoxicity assay. Fifteen minutes after rHDL infusion, there was a significant difference in ex-vivo-induced TNF activity between groups (750 +/- 160, 170 +/- 40, 80 +/- 30, 60 +/- 30 pg TNF/ml, for the control, 25, 50, and 75 mg/kg rHDL dose groups, respectively; P < 0.0001). The duration of ex-vivo TNF inhibition was dependent on the dose of rHDL. Even at 2 hr, rHDL showed a pronounced TNF inhibition (control: 950 +/- 120 pg TNF/ml; 75 mg/kg: 140 +/- 60 pg TNF/ml). Further studies showed that a prophylactic infusion of rHDL diminished LPS-induced TNF production in a rabbit endotoxemia model.(ABSTRACT TRUNCATED AT 250 WORDS)
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Lipopolissacarídeos/farmacologia , Lipoproteínas HDL/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Animais , Relação Dose-Resposta a Droga , Endotoxinas/sangue , Masculino , Coelhos , Proteínas Recombinantes , Choque Séptico/fisiopatologia , Fatores de TempoRESUMO
To study the changes in the hippocampal cholinergic system of chronologically old and behaviorally impaired animals, old (21 months of age) and young (3 months of age) male, Fischer-344 rats were used. The aged animals were tested on a reference memory task (Morris water maze) and found to be functionally impaired as compared to the young controls. Carbachol-stimulated phosphoinositide metabolism was measured in hippocampal slices from young and old rats. Slices were prelabeled with 3H-inositol for 120 min and subjected to muscarinic stimulation in the presence of lithium. Following extraction of the slices with acidified solvent mixture, the inositolphosphates present in the aqueous fraction were isolated by ion exchange chromatography. Receptor-stimulated release of inositolphosphates (IPs) was found to be increased in the hippocampus of older animals. This age-related enhancement of IP release was in contrast to the decrease in choline acetyltransferase (CHAT) activity in the hippocampus. We postulate that alterations in the G-protein coupling with the muscarinic receptor leads to an increase in the phosphoinositide turnover in part as a compensatory mechanism for neuronal cell death and reduced transmitter levels.
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Envelhecimento/metabolismo , Hipocampo/metabolismo , Fosfatidilinositóis/metabolismo , Receptores Muscarínicos/metabolismo , Envelhecimento/fisiologia , Animais , Carbacol/farmacologia , Colina O-Acetiltransferase/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Hipocampo/efeitos dos fármacos , Cinética , Aprendizagem/fisiologia , Masculino , Quinuclidinil Benzilato/metabolismo , Ratos , Ratos Endogâmicos F344 , Receptores Muscarínicos/efeitos dos fármacosRESUMO
Male, Fischer-344 rats were pretreated with MK-801 (0.1, 1.0 or 10.0 mg/kg, i.p.) prior to bilateral injection of kainate (0.33 micrograms/site) into the dorsal and ventral hippocampus. Kainate impaired the acquisition of a water maze acquisition task 4 weeks after surgery, an effect not attenuated by pretreatment with MK-801. However, higher doses (1.0 and 10.0 mg/kg) of MK-801 reduced the amount of kainate-induced granule cell and to some extent CA1 pyramidal cell damage in the hippocampus. Kainate-induced CA3/CA4 damage was not affected by MK-801 pretreatment. MK-801 (10 mg/kg) also reduced the amount of thalamic damage produced by kainate. These data support the conclusion that intrahippocampal kainate-induced destruction of CA3/CA4 pyramidal cells is mediated by non-N-methyl-D-aspartate (non-NMDA) receptors and that kainate-induced loss of these cells is associated with the neurobehavioral effects of intrahippocampally administered kainate.
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Dibenzocicloeptenos/farmacologia , Hipocampo/fisiologia , Ácido Caínico/toxicidade , Aprendizagem/efeitos dos fármacos , Receptores de Neurotransmissores/fisiologia , Animais , Maleato de Dizocilpina , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos , Ratos Endogâmicos F344 , Receptores de N-Metil-D-Aspartato , Receptores de Neurotransmissores/efeitos dos fármacosRESUMO
Male Fischer-344N rats were pretreated bilaterally with intrahippocampal (D) (-)-2-amino-7-phosphonoheptanoic acid [(D)-2-APH] (2.5, 5.0 and 10 micrograms/site), a competitive N-methyl-d-aspartate (NMDA) antagonist, prior to the administration of bilateral N-MDA (10 micrograms/site). (D)-2-APH completely attenuated NMDA-induced hyperactivity and water maze acquisition deficits. (D)-2-APH also attenuated hippocampal pyramidal and granule cell loss induced by NMDA. These effects were stereospecific since pretreatment of the isomer L-(+)-2-APH (10 micrograms/site) had no effect on hyperactivity and water maze acquisition deficits produced by NMDA. In addition, (L)-2-APH provided no protection from NMDA-induced hippocampal granule and pyramidal cell loss. Together, these results suggest that the intrahippocampal administration of NMDA might serve as a useful in vivo model for evaluating the effects associated with the overactivation of NMDA receptors.
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2-Amino-5-fosfonovalerato/análogos & derivados , Ácido Aspártico/análogos & derivados , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Aminoácidos/farmacologia , Animais , Ácido Aspártico/antagonistas & inibidores , Ácido Aspártico/toxicidade , Hipocampo/patologia , Aprendizagem/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , N-Metilaspartato , Ratos , Ratos Endogâmicos F344 , EstereoisomerismoRESUMO
The ventral hippocampi of male, Fischer-344 rats were implanted with microdialysis probes and the effects of systemically administered kainic acid (KA) (8 mg/kg, s.c.) on the in vivo release of amino acids were measured for four hours after administration. In order to measure GABA release in vivo, gamma-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase, was injected intrahippocampally prior to perfusion. GVG pretreatment resulted in measurable levels of GABA in the perfusate without significant effects on the release of aspartate, glutamate, glutamine, glycine or taurine. Following GVG pretreatment systemic administration of KA produced a time-dependent increase in GABA, as well as all other amino acids except glutamine, which was initially decreased. These results show for the first time that systemically administered KA increases extracellular GABA levels, an effect previously reported only in vitro. These data suggest that prior to destruction of GABA-containing interneurons in the hippocampus, there is an increased activity of those GABA interneurons reflected as an increase in extracellular GABA levels.
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Hipocampo/metabolismo , Ácido Caínico/farmacologia , Ácido gama-Aminobutírico/metabolismo , Aminoácidos/metabolismo , Animais , Hipocampo/efeitos dos fármacos , Injeções Subcutâneas , Ácido Caínico/administração & dosagem , Cinética , Masculino , Ratos , Ratos Endogâmicos F344 , Valores de Referência , Fatores de TempoRESUMO
Several reports have implicated the overactivity of hippocampal glutaminergic systems in neurodegenerative conditions including Senile dementia of the Alzheimer's type (SDAT). The neurobiological effects of hippocampal glutaminergic hyperactivity were studied by perforant pathway stimulation. Forty-five minutes of sustained perforant pathway stimulation produced a 50% or greater increase in motor activity 1, 2, and 3 weeks after stimulation. Robust retention deficits in a 48-h step-through passive avoidance task were evident 2 weeks post-stimulation. Furthermore, animals receiving stimulation were impaired in the acquisition of a spatial task in the Morris water maze. Stimulated animals exhibited little reduction in their escape latencies over the testing period. The learning and memory deficits were associated with a loss of CA1 and CA3 pyramidal cells and pretreatment with the N-methyl-D-aspartate antagonist MK-801 reduced this cell loss, particularly in the CA1 region of the hippocampus. These results suggest that sustained stimulation of the perforant pathway may be useful in studying neurological deficits associated with glutaminergic hyperfunction.
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Glutamina/fisiologia , Hipocampo/fisiologia , Animais , Aprendizagem da Esquiva/fisiologia , Estimulação Elétrica , Hipocampo/citologia , Masculino , Memória/fisiologia , Atividade Motora/fisiologia , Vias Neurais/fisiologia , Ratos , Ratos Endogâmicos F344RESUMO
The overstimulation of receptors for L-glutamate, particularly those of the N-methyl-D-aspartate (NMDA) type, has been suggested to play a role in mediating damage in a variety of neurodegenerative conditions or disorders ranging from ischemia/hypoxia to senile dementia of the Alzheimer's type (SDAT). We report here that the functional deficits and histological damage mediated by the overactivation of NMDA receptors in the Fischer 344 rat hippocampus can be blocked effectively by systemic administration of the noncompetitive NMDA antagonist, MK-801. These results suggest that MK-801 may be effective clinically in attenuating memory loss and hippocampal damage in disorders associated with the overstimulation of NMDA receptors.
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Ácido Aspártico/análogos & derivados , Comportamento Animal/efeitos dos fármacos , Transtornos Cognitivos/prevenção & controle , Dibenzocicloeptenos/farmacologia , Hipocampo/efeitos dos fármacos , Receptores de Neurotransmissores/efeitos dos fármacos , Animais , Ácido Aspártico/antagonistas & inibidores , Transtornos Cognitivos/induzido quimicamente , Maleato de Dizocilpina , Hipocampo/patologia , Masculino , N-Metilaspartato , Ratos , Ratos Endogâmicos F344 , Receptores de N-Metil-D-AspartatoRESUMO
Evidence is accumulating which suggests that brain damage associated with certain neurodegenerative conditions may be at least partially produced by the overactivation of N-methyl-D-aspartate receptors (N-MDA). To systematically examine the overactivation of N-MDA receptors, N-MDA was administered directly to the frontal cortex and to the hippocampus in rats. It was found that cortical application (1, 2, or 4 mg) had no effect on motor activity 1, 2, or 3 wk after surgery. Four mg N-MDA failed to affect acquisition of a water maze task despite large decreases in cortical width at the site of application. In addition, no alterations in striatal, hippocampal, or cortical cholineacetyltransferase (CHAT) activity were detected after cortical application. Intrahippocampal N-MDA (0, 2.5, 5.0, 10.0, 20.0 micrograms/site) increased motor activity in a dose dependent manner 1, 2, and 3 wk post-surgery. Furthermore, 10 micrograms/site significantly impaired water maze acquisition. Intrahippocampal N-MDA also increased hippocampal CHAT activity and resulted in a loss of pyramidal and dentate granule cells. These results suggest that N-MDA may serve as a useful tool in studying the effects of glutaminergic hyperfunction and its role in neurodegenerative disorders which involve the overactivation of N-MDA receptors.
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Ácido Aspártico/análogos & derivados , Animais , Ácido Aspártico/administração & dosagem , Ácido Aspártico/toxicidade , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/patologia , Colina O-Acetiltransferase/metabolismo , Hipocampo/enzimologia , Masculino , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , N-Metilaspartato , Tratos Piramidais/citologia , Ratos , Ratos Endogâmicos F344RESUMO
Rats were given bilateral injections of colchicine into the area of the nucleus basalis. Colchicine produced dose-dependent alterations in the acquisition of a food-reinforced working-memory task. Colchicine-induced deficits in maze performance were attenuated by cholinergic agents, including physostigmine, RS-86 (2-ethyl-8-methyl-2,8-diazospiro-(4,5)-decan-1,3-dione-hydro bromide) and nicotine. Naloxone and vasopressin did not affect radial-arm maze performance of colchicine-treated rats. Subsequent neurochemical analysis showed that colchicine decreased choline acetyltransferase (ChAT) activity and levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the neocortex. However, ChAT activity and other neurochemical measures were not altered in the hippocampus or corpus striatum. Histological assessment indicated damage limited to the injection in the area of the nucleus basalis and enlarged cerebrolateral ventricles. These data suggest the possible utility of the colchicine model in the study of cognitive deficits associated with neurodegenerative diseases.
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Gânglios da Base/fisiologia , Colchicina/farmacologia , Memória/fisiologia , Parassimpatomiméticos/farmacologia , Receptores Colinérgicos/fisiologia , Animais , Gânglios da Base/efeitos dos fármacos , Aminas Biogênicas/metabolismo , Relação Dose-Resposta a Droga , Masculino , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Nicotina/farmacologia , Fisostigmina/farmacologia , Ratos , Ratos Endogâmicos F344 , Receptores Colinérgicos/efeitos dos fármacos , Succinimidas/farmacologiaRESUMO
Rats were given bilateral injections of colchicine into the dorsal and ventral hippocampus. Behavioral, neurochemical and histopathological measurements were taken, up to 12 weeks after surgery. Colchicine produced a consistent increase in spontaneous motor activity, enhanced acoustic startle reactivity, and accelerated acquisition of two-way shuttle box avoidance, but did not affect reactivity to a noxious thermal stimulus. Measurement of dynorphin in the hippocampus indicated that colchicine rapidly depleted this neuropeptide, which is thought to be contained preferentially in the mossy fibers of granule cells of the hippocampus. Colchicine also decreased Met-enkephalin in the hippocampus, but the magnitude of the change (22%) was less than that (89% depletion) observed for hippocampal dynorphin. Examination of hippocampal morphology using light microscopic techniques indicated that colchicine caused approximately 60% degeneration of granule cells in the hippocampus. Although the length of the pyramidal cells was decreased (12-16%), the width of the CA1 and CA3 region of the hippocampus was not affected. These data underscore the importance of the granule cells in the mediation of behavioral processes such as motor activity, startle reactivity and performance of shuttle box avoidance.