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1.
J Environ Sci (China) ; 123: 255-269, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521988

RESUMO

Ambient air quality standards are the core strategic goal of ambient air quality management. Countries worldwide have given importance to research on the development of ambient air quality standards. To understand the history of the development of China's ambient air quality standards, this study analyzed the background associated with all previous formulations and revisions of the standards, classification of functional areas, standard grading, pollutants, and evolution of the standard limits over the past 40 years. The results show that since the initial release of the "Ambient Air Quality Standard" by China in 1982, it has been supplemented once, revised twice, and modified twice. The first ambient air quality standard specified the standard limits of six pollutants commonly found in ambient air. With the development of ambient air quality management, the number of pollutants has increased to ten. Since the release of the "Ambient Air Quality Standards" in 2012, the ambient air quality in China has significantly improved. However, the proportion of cities meeting these standards is still low. At present, China is suitably positioned to make the standards associated with 24 hr SO2 concentrations more stringent such that it meets the values defined in the World Health Organization (WHO) interim target-2 and the WHO air quality guideline (AQG). We further suggested that the SO2 standard should be revised promptly. Simultaneously, regions with a relatively high proportion of cities meeting the standard are encouraged to introduce more stringent interim target limits in due course to manage the local ambient air quality.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/análise , Cidades , China
2.
Sensors (Basel) ; 22(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36081144

RESUMO

Chip pad inspection is of great practical importance for chip alignment inspection and correction. It is one of the key technologies for automated chip inspection in semiconductor manufacturing. When applying deep learning methods for chip pad inspection, the main problem to be solved is how to ensure the accuracy of small target pad detection and, at the same time, achieve a lightweight inspection model. The attention mechanism is widely used to improve the accuracy of small target detection by finding the attention region of the network. However, conventional attention mechanisms capture feature information locally, which makes it difficult to effectively improve the detection efficiency of small targets from complex backgrounds in target detection tasks. In this paper, an OCAM (Object Convolution Attention Module) attention module is proposed to build long-range dependencies between channel features and position features by constructing feature contextual relationships to enhance the correlation between features. By adding the OCAM attention module to the feature extraction layer of the YOLOv5 network, the detection performance of chip pads is effectively improved. In addition, a design guideline for the attention layer is proposed in the paper. The attention layer is adjusted by network scaling to avoid network characterization bottlenecks, balance network parameters, and network detection performance, and reduce the hardware device requirements for the improved YOLOv5 network in practical scenarios. Extensive experiments on chip pad datasets, VOC datasets, and COCO datasets show that the approach in this paper is more general and superior to several state-of-the-art methods.


Assuntos
Algoritmos , Redes Neurais de Computação
3.
J Environ Sci (China) ; 55: 339-353, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28477830

RESUMO

To compare the inorganic chemical compositions of TSP (total suspended particulate), PM10 (particulate matter with an aerodynamic diameter less than 10µm) and PM2.5 (particulate matter with an aerodynamic diameter less than 2.5µm) in southern and northern cities in China, atmospheric particles were synchronously collected in Dalian (the northern city) and Xiamen (the southern city) in spring and autumn of 2004. The mass concentrations, twenty-three elements and nine soluble ions were assessed. The results show that in Dalian, the mass concentrations of Mg, Al, Ca, Mn and Fe in spring were 4.0-10.1, 2.6-8.0, 4.1-12, 1.2-3.6 and 2.9-7.9 times higher, respectively, than those in Xiamen. The dust storm influence is more obvious in Dalian in spring. However, in Xiamen, heavy metals accounted for 13.9%-17.9% of TSP, while heavy metals contributed to 5.5%-9.3% of TSP in Dalian. These concentrations suggest that heavy metal pollution in Xiamen was more serious. In addition, the concentrations of Na+, Cl-, Ca2+ and Mg2+ were higher in Dalian due to the influence of marine aerosol, construction activities and soil dust. The NO3-/SO42- ratios in Dalian (0.25-0.49) were lower than those in Xiamen (0.51-0.62), indicating that the contributions of vehicle emission to particles in Xiamen were higher. Coefficient of divergence values was higher than 0.40, implying that the inorganic chemical composition profiles for the particles of Dalian and Xiamen were quite different from each other.


Assuntos
Poluentes Atmosféricos/análise , Atmosfera/química , Monitoramento Ambiental , Material Particulado/análise , Poluentes Atmosféricos/química , China , Cidades , Tamanho da Partícula , Emissões de Veículos/análise
4.
Dyslexia ; 22(4): 362-378, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27805322

RESUMO

Reading depends heavily on the efficient shift of attention. Mounting evidence has suggested that dyslexics have deficits in covert attentional shift. However, it remains unclear whether dyslexics also have deficits in overt attentional shift. With the majority of relevant studies carried out in alphabetic writing systems, it is also unknown whether the attentional deficits observed in dyslexics are restricted to a particular writing system. The present study examined inhibition of return (IOR)-a major driving force of attentional shifts-in dyslexic children learning to read a logographic script (i.e., Chinese). Robust IOR effects were observed in both covert and overt attentional tasks in two groups of typically developing children, who were age- or reading ability-matched to the dyslexic children. In contrast, the dyslexic children showed IOR in the overt but not in the covert attentional task. We conclude that covert attentional shift is selectively impaired in dyslexic children. This impairment is not restricted to alphabetic writing systems, and it could be a significant contributor to the difficulties encountered by children learning to read. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Atenção , Dislexia/psicologia , Idioma , Leitura , Estudos de Casos e Controles , Criança , China , Feminino , Humanos , Inibição Psicológica , Masculino , Redação
5.
Water Environ Res ; 87(11): 1941-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26564582

RESUMO

The real-time polymerase chain reaction was used to quantitatively evaluate distribution patterns and nitrogen removal pathways of the amoA, nxrA, narG, napA, nirK, qnorB, nosZ, nas, and nifH genes and 16S rRNA in anaerobic ammonia oxidation bacteria in four multimedia constructed wetlands for rural wastewater treatment. The results indicated that the abundance of functional genes for nitrogen removal in the rhizosphere layer (0 to 30 cm), water distribution layer (30 to 50 cm), multime filler layer (50 to 130 cm), and catchment layer (130 to 170 cm) of the constructed wetlands were closely related. The rhizosphere layer was conducive to the absolute enrichment of dominant genes. The other three layers were favorable to the relative enrichment of rare genes.


Assuntos
Genes Bacterianos , Nitrogênio/metabolismo , RNA Ribossômico 16S/análise , Purificação da Água , Áreas Alagadas , Amônia/metabolismo , Anaerobiose , Bactérias Anaeróbias/genética , Nitrogênio/isolamento & purificação , Oxirredução , Águas Residuárias/microbiologia
6.
Gene ; 855: 147103, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36513191

RESUMO

B-GATA transcription factors with the LLM domain (LLM-domain B-GATAs) play important roles in developmental processes and environmental responses in flowering plants. Their characterization can therefore provide insights into the structural and functional evolution of functional gene families. Phylogenetic and sequence analysis suggests that LLM-domain B-GATAs evolved from ancestral GATA transcription factors before the divergence of chlorophyte algae and Streptophyta. We compared the function of PpGATA1, a LLM-domain B-GATA gene in moss Physcomitrium patens, with Arabidopsis thaliana counterparts and showed that, in P. patens, PpGATA1 controls growth and greening in haploid gametophytes, while in transgenic Arabidopsis it affects germination, leaf development, flowering time, greening and light responses in diploid sporophytes. These PpGATA1 functions are similar to those of Arabidopsis counterparts, AtGNC, AtGNL and AtGATA17. PpGATA1 was able to complement the role of GNC and GNL in a gnc gnl double mutant, and the LLM domains of PpGATA1 and GNC behaved similarly. The functions of LLM-domain B-GATAs regulating hypocotyl elongation and cotyledon epinasty in flowering plants pre-exist before the divergence of mosses and the lineage leading to flowering plants. This study sheds light on adaption of PpGATA1 and its homologs to new developmental designs during the evolution.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Briófitas , Bryopsida , Fatores de Transcrição GATA/genética , Proteínas de Arabidopsis/genética , Filogenia , Briófitas/genética , Bryopsida/genética
7.
Front Psychol ; 13: 849097, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35619786

RESUMO

The sudden arrival of COVID-19 has had an enormous impact on the lives of people around the world, including significant psychological pressure and increased emotional needs. In China, research into user psychology and the motivations of commercial digital media has become more popular, but the national media should pay more attention to user psychology and perform more research on user motivations to improve the effectiveness of communication. We investigated people's internal psychology and motivation for using national media digital platforms in China during the pandemic. We collected data through online questionnaires and analyzed the use of apps of CCTV and The People's Daily by individual users during the pandemic and the psychological needs of national digital media users. In the first stage of our research, we selected national digital media app users through the WeChat platform. In the second stage, more active users were chosen by snowballing upon the original sample. We surveyed 210 participants and ultimately obtained 180 valid samples. We analyzed the data using used SPSS 23.0. The results showed that with the help of digital media platforms and diversified media technology, the Chinese national media not only met the needs of users for information acquisition, but also provided sufficient emotional mutual assistance and comfort to users through the network aggregation formed by digital scene communication.

8.
Front Hum Neurosci ; 16: 919465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248689

RESUMO

The noisy computation hypothesis of developmental dyslexia (DD) is particularly appealing because it can explain deficits across a variety of domains, such as temporal, auditory, phonological, visual and attentional processes. A key prediction is that noisy computations lead to more variable and less stable word representations. A way to test this hypothesis is through repetition of words, that is, when there is noise in the system, the neural signature of repeated stimuli should be more variable. The hypothesis was tested in an functional magnetic resonance imaging experiment with dyslexic and typical readers by repeating words twelve times. Variability measures were computed both at the behavioral and neural levels. At the behavioral level, we compared the standard deviation of reaction time distributions of repeated words. At the neural level, in addition to standard univariate analyses and measures of intra-item variability, we also used multivariate pattern analyses (representational similarity and classification) to find out whether there was evidence for noisier representations in dyslexic readers compared to typical readers. Results showed that there were no significant differences between the two groups in any of the analyses despite robust results within each group (i.e., high representational similarity between repeated words, good classification of words vs. non-words). In summary, there was no evidence in favor of the idea that dyslexic readers would have noisier neural representations than typical readers.

9.
Bioresour Technol ; 361: 127604, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35835421

RESUMO

The combined effects of carbon source (HAc, HPr, Glu, Glu + HAc) and nitrate concentration (40, 80 mg/L labeling as R40, R80) on partial denitrification (PD) were discussed at C/N ratio of 2.5 (COD = 100, 200 mg/L). The optimal NO2--N and NTR reached to 67.03 mg/L, 99.14% in HAc-R80 system, and denitrification kinetics revealed the same conclusion, corresponding to higher COD utilization rate (CUR: 58.46 mgCOD/(gVSS·h)), nitrate reduction rate (NaRR: 29.94 mgN/(gVSS·h)) and nitrite accumulation rate (NiAR: 29.68 mgN/(gVSS·h)). The preference order was HAc > HPr > Glu + HAc > Glu in both R40 and R80 systems due to different metabolic pathways, however, the NO2--N accumulation and kinetic parameters of R80 group were dramatically higher than those in R40 for the same carbon source. The R80 group facilitated more concentrated biodiversity (607-808 OTUs) with Terrimonas and norank_f_Saprospiraceae responsible for high NO2--N accumulation in HAc and HPr served systems, while norank_f_norank_o_Saccharimonadales and OLB13 dominated the Glu containing systems.


Assuntos
Nitratos , Nitritos , Reatores Biológicos , Carbono/metabolismo , Desnitrificação , Cinética , Nitratos/metabolismo , Nitritos/metabolismo , Nitrogênio/metabolismo , Dióxido de Nitrogênio , Óxidos de Nitrogênio , Esgotos
10.
Psych J ; 11(4): 448-459, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35599334

RESUMO

Face processing is known to decline in older adults; however, a clear understanding of the brain networks behind this cognitive decline is still lacking. In this study, we investigated the neural correlates of the declined face processing with aging from a resting-state brain network perspective. Nineteen healthy old adults and 22 young adults were recruited and underwent two functional magnetic resonance imaging (fMRI) scanning sessions (i.e., resting-state and localizer task) and two behavioral tests (face matching and symbol-form matching). We examined age-related alterations in resting-state functional connectivity (FC) within face network as well as between face network and other networks, and tested their associations with behavioral performance of face and symbol-form processing. We found that (a) compared with young adults, old adults exhibited decreased FC between face-selective regions (fusiform face area and occipital face area), but increased FC between face-selective regions and non-face-selective regions; (b) these age-related FC alterations were correlated with individuals' behavioral performance of face and symbol-form processing. Collectively, these findings suggest the declines of face processing are associated with a mixture of decreased integration within the face network and segregation beyond the face network in the aging brain, and provide evidence for a neural basis of cognitive aging in face processing from an intrinsic brain network perspective.


Assuntos
Envelhecimento , Reconhecimento Facial , Idoso , Envelhecimento/psicologia , Encéfalo , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética/métodos , Adulto Jovem
11.
Neuropsychologia ; 138: 107343, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952981

RESUMO

Developmental dyslexia is known to involve dysfunctions in multiple brain regions; however, a clear understanding of the brain networks behind this disorder is still lacking. The present study examined the functional network connectivity in Chinese dyslexic children with resting-state electroencephalography (EEG) recordings. EEG data were recorded from 27 dyslexic children and 40 age-matched controls, and a minimum spanning tree (MST) analysis was performed to examine the network connectivity in the delta, theta, alpha, and beta frequency bands. The results show that, compared to age-matched controls, Chinese dyslexic children had global network deficiencies in the beta band, and the network topology was more path-like. Moderate correlations are observed between MST degree metric and rapid automatized naming and morphological awareness tests. These observations, together with the findings in alphabetic languages, show that brain network deficiency is a common neural underpinning of dyslexia across writing systems.


Assuntos
Ondas Encefálicas/fisiologia , Dislexia/fisiopatologia , Eletroencefalografia , Neuroimagem Funcional , Rede Nervosa/fisiopatologia , Criança , China , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Psicolinguística , Descanso
12.
Huan Jing Ke Xue ; 41(7): 3121-3129, 2020 Jul 08.
Artigo em Zh | MEDLINE | ID: mdl-32608884

RESUMO

Based on the NOx emission information of 671 coal-fired power units, the NOx emission characteristics of non-ultra-low-emission (non-ULE) and ultra-low-emission (ULE) coal-fired power units during the start-up process were compared and analyzed. The results showed that in the start-up stage of non-ULE units, the exceeding standard rate (ESR) of NOx emission concentration was 81.53%, the average exceeding standard hours (ESHs) was 2.64 h, and the average maximum emission hourly mean concentration (MEHC) was 284.06 mg·m-3. The NOx ESR of ULE units was 79.86%, the average ESHs was 2.52 h, and the average MEHC was 231.61 mg·m-3. There was no significant difference in the ESR and the average ESHs between non-ULE and ULE units, but the difference in the average MEHC was significant. There was no significant difference in the ESR, average ESHs, and average MEHC between different grades of non-ULE units, except that the average MEHC of 300 MW units was significantly lower than that of 200 MW units. There was statistical difference in the ESR, average ESHs, and average MEHC among different grades of ULE units, and 600 MW units performed best in the ESHs control, whereas 1000 MW units performed best in the emission concentration control.

13.
Neurosci Bull ; 34(3): 517-526, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29589216

RESUMO

The process of reading words depends heavily on efficient visual skills, including analyzing and decomposing basic visual features. Surprisingly, previous reading-related studies have almost exclusively focused on gross aspects of visual skills, while only very few have investigated the role of finer skills. The present study filled this gap and examined the relations of two finer visual skills measured by grating acuity (the ability to resolve periodic luminance variations across space) and Vernier acuity (the ability to detect/discriminate relative locations of features) to Chinese character-processing as measured by character form-matching and lexical decision tasks in skilled adult readers. The results showed that Vernier acuity was significantly correlated with performance in character form-matching but not visual symbol form-matching, while no correlation was found between grating acuity and character processing. Interestingly, we found no correlation of the two visual skills with lexical decision performance. These findings provide for the first time empirical evidence that the finer visual skills, particularly as reflected in Vernier acuity, may directly contribute to an early stage of hierarchical word processing.


Assuntos
Percepção de Forma/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Leitura , Semântica , Acuidade Visual/fisiologia , Vocabulário , Adolescente , Tomada de Decisões , Feminino , Humanos , Masculino , Estimulação Luminosa , Estatística como Assunto , Adulto Jovem
14.
Oncol Lett ; 15(2): 2550-2554, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434972

RESUMO

The present study aimed to investigate the effect of tanshinone II, isolated from Salvia miltiorrhiza Bunge, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Male Sprague-Dawley rats were divided into three groups: Control, LPS and tanshinone II. Animals in the tanshinone II and LPS groups were administered 10 mg/kg LPS, whereas those in the control group received an equal volume of normal saline. Tanshinone II treatment group were injected with 30 nm/kg tanshinone II at 1 h after LPS administration. The results revealed that LPS administration increased the bronchoalveolar lavage fluid protein concentration significantly compared with the control group. However, tanshinone II treatment significantly inhibited the LPS-induced increase in protein level. Treatment of the LPS-administered rats with tanshinone II prevented the formation of pulmonary edema, which was evidenced by low values for wet to dry lung weight ratio. The activity of myeloperoxidase and expression of malondialdehyde were significantly lower in lung homogenates from the tanshinone II group compared with the LPS group. Furthermore, tanshinone II treatment inhibited the expression of tumor necrosis factor-α and interleukin-6 in the blood plasma. Tissue sections of the tanshinone II group exhibited normal morphology and absence of neutrophil accumulation. However, in the LPS group, neutrophils accumulated and penetrated into the pulmonary tissues. These results suggested that tanshinone II protects the rats from LPS-induced ALI. Therefore tanshinone II may have clinical applications in the treatment of ALI.

15.
Psychophysiology ; 54(8): 1128-1137, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28369927

RESUMO

Neuroimaging and neuropsychological studies have identified the involvement of the right posterior region in the processing of visual words. Interestingly, in contrast, ERP studies of the N170 typically demonstrate selectivity for words more strikingly over the left hemisphere. Why is right hemisphere selectivity for words during the N170 epoch typically not observed, despite the clear involvement of this region in word processing? One possibility is that amplitude differences measured on averaged ERPs in previous studies may have been obscured by variation in peak latency across trials. This study examined this possibility by using single-trial analysis. Results show that words evoked greater single-trial N170s than control stimuli in the right hemisphere. Additionally, we observed larger trial-to-trial variability on N170 peak latency for words as compared to control stimuli over the right hemisphere. Results demonstrate that, in contrast to much of the prior literature, the N170 can be selective to words over the right hemisphere. This discrepancy is explained in terms of variability in trial-to-trial peak latency for responses to words over the right hemisphere.


Assuntos
Córtex Cerebral/fisiologia , Potenciais Evocados Visuais/fisiologia , Lateralidade Funcional/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Reconhecimento Psicológico/fisiologia , Adolescente , Eletroencefalografia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Leitura , Adulto Jovem
16.
Bioresour Technol ; 102(2): 550-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20797854

RESUMO

A multi-media biological aerated filter (MBAF) with clinoptilolite media was used to treat synthetic wastewater. Coal ash bioceramsite with supplemental metallic iron was added to the clinoptilolite media of MBAFs in a brick-wall embedded design. Performance parameters, such as hydraulic, organic, N and P loading capacity and microbial community composition were studied for different quantity of supplemental metallic iron contained in three MBAFs. The MBAFs with more metallic iron were found to have superior hydraulic and organic loading, and higher N and P capacities. COD, NH3-N and TP removal dropped by 7-10%, 6-7% and 4-5%, respectively, with when hydraulic loading was raised from 2.8 to 7.5 m3 m(-2) d(-1). NH3-N removal also decreased 8-9% when ammonia loading was elevated from 0.078 to 0.156 kg NH3-N m(-3) d(-1). Real-time PCR revealed a relatively stable bacterial community composed primarily of eubacteria that formed after an initial 120 d operational period. Doubling the amount of metallic iron in the bioceramsite media resulted in a twofold increase of eubacteria in the MBAF, but a decrease in the ratio of anaerobic ammonia-oxidizing bacteria to total bacteria.


Assuntos
Bactérias/metabolismo , Carvão Mineral , Filtração/instrumentação , Purificação da Água/instrumentação , Purificação da Água/métodos , Zeolitas/química , Aerobiose , Amônia/isolamento & purificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Sequência de Bases , Biodegradação Ambiental , Biodiversidade , Análise da Demanda Biológica de Oxigênio , DNA Ribossômico/genética , Eletroforese em Gel de Gradiente Desnaturante , Desenho de Equipamento , Nitrogênio/isolamento & purificação , Fósforo/análise , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Água/química
17.
Bioresour Technol ; 101(1): 174-80, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19733065

RESUMO

Status of, and changes in, the bacterial communities at two acclimation stages (with- and without-ultrasound) in a small 70 degrees C ultrasound-enhanced anaerobic reactor for treating carbazole-containing wastewater reactor were analyzed by PCR-DGGE and real-time PCR techniques. PCR-DGGE results indicated that a large number of bands occurred in the whole sludge samples. Pseudomonas sp., Comamonas sp., and Diaphorobacter sp. were identified as being able to utilize carbazole as a carbon source, survive in an anaerobic and ultra-high-temperature environment and become dominant bacterial taxa during the with-ultrasound stage in the reactor. Total bacterial density in the with-ultrasonic stages was 10 x higher than in the without-ultrasonic treatment. The proportion of Pseudomonas was relatively stable at 0.13%-0.15% in both acclimation stages, which indicates that Pseudomonas can flourish and promote carbazole degradation either with or without-ultrasound. These studies provide information on carbazole degradation under ultra-high-temperature conditions in an anaerobic environment.


Assuntos
Bactérias Anaeróbias/classificação , Bactérias Anaeróbias/metabolismo , Reatores Biológicos/microbiologia , Carbazóis/metabolismo , Esgotos/microbiologia , Sonicação/métodos , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Bactérias Anaeróbias/genética , Temperatura , Microbiologia da Água
18.
Invest Ophthalmol Vis Sci ; 49(11): 5094-102, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18599562

RESUMO

PURPOSE: To define the molecular pharmacology underlying the antiangiogenic effects of nonpeptide imidazolidine-2,4-dione somatostatin receptor agonists (NISAs) and evaluate the efficacy of NISA in ocular versus systemic delivery routes in ocular disease models. METHODS: Functional inhibitory effects of the NISAs and the somatostatin peptide analogue octreotide were evaluated in vitro by chemotaxis, proliferation, and tube-formation assays. The oxygen-induced retinopathy (OIR) model and the laser model of choroidal neovascularization (CNV) were used to test the in vivo efficacy of NISAs. Transscleral permeability of a candidate NISA was also measured. RESULTS: NISAs inhibited growth factor-induced HREC proliferation, migration and tube formation with submicromolar potencies (IC(50), 0.1-1.0 microM) comparable to octreotide. In the OIR model, systemic administration of the NISAs RFE-007 and RFE-011 inhibited retinal neovascularization in a dose-dependent manner, comparable to octreotide. In the CNV model, intravitreal RFE-011 resulted in a 56% reduction (P < 0.01) in CNV lesion area, whereas systemic administration resulted in a 35% reduction (P < 0.05) in lesion area. RFE-011 demonstrated transscleral penetration. CONCLUSIONS: Micromolar concentrations of octreotide and NISAs are necessary for antiangiogenic effects, whereas nanomolar concentrations are effective for endocrine inhibition. This suggests that the antiangiogenic activity of NISAs and octreotide is mediated by an overall much less efficient downstream coupling mechanism than is growth hormone release. As a result, the intravitreal or transscleral route of administration should be seriously considered for future clinical studies of SSTR2 agonists used for treatment of ocular neovascularization to ensure efficacious concentrations in the target retinal and choroidal tissue.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Expressão Gênica/efeitos dos fármacos , Imidazolidinas/agonistas , RNA/genética , Receptores de Somatostatina/genética , Neovascularização Retiniana/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacocinética , Animais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/uso terapêutico , Autorradiografia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Progressão da Doença , Relação Dose-Resposta a Droga , Humanos , Injeções , Camundongos , Camundongos Endogâmicos C57BL , Octreotida/administração & dosagem , Octreotida/farmacocinética , Octreotida/uso terapêutico , Soluções Oftálmicas , Reação em Cadeia da Polimerase , Coelhos , Receptores de Somatostatina/metabolismo , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Esclera , Resultado do Tratamento , Corpo Vítreo
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