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1.
Redox Biol ; : 101469, 2020 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-32362442

RESUMEN

Iron has been implicated in the pathogenesis of retinal degenerative diseases, including ocular siderosis. However, the mechanisms of iron-induced retinal toxicity are incompletely understood. Previous work shows that intravitreal injection of Fe2+ leads to photoreceptor (PR) oxidative stress, resulting in PR death within 14 days, and cones are more susceptible than rods to iron-induced oxidative damage. In order to further investigate the mechanism of intravitreal iron-induced retinal toxicity and shed light on mechanisms of iron-induced retinopathy in other mouse models, Fe2+, Fe3+, or saline were injected into the vitreous of adult wild-type mice. Pre-treatment with Ferrostatin-1 was used to investigate whether iron-induced retinal toxicity resulted from ferroptosis. Color and autofluorescence in vivo retinal imaging and optical coherence tomography were performed on day 2 and day 7 post-injection. Eyes were collected for quantitative PCR and Western analysis on day 1 and for immunofluorescence on both day 2 and 7. In vivo imaging and immunofluorescence revealed that Fe2+, but not Fe3+, induced PR oxidative damage and autofluorescence on day 2, resulting in PR death and retinal pigment epithelial cell (RPE) autofluorescence on day 7. Quantitative PCR and Western analysis on day 1 indicated that both Fe2+ and Fe3+ induced iron accumulation in the retina. However, only Fe2+ elevated levels of oxidative stress markers and components of ferroptosis in the retina, and killed PRs. Ferrostatin-1 failed to protect the retina from Fe2+-induced oxidative damage. To investigate the mechanism of Fe2+-induced RPE autofluorescence, rd10 mutant mice aged 6 weeks, with almost total loss of PRs, were given intravitreal Fe2+ or Fe3+ injections: neither induced RPE autofluorescence. This result suggests Fe2+-induced RPE autofluorescence in wild-type mice resulted from phagocytosed, oxidized outer segments. Together these data suggest that intraretinal Fe2+ causes PR oxidative stress, leading to PR death and RPE autofluorescence.

3.
Sci Total Environ ; 700: 134536, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31689651

RESUMEN

Heterogeneous electro-Fenton (EF) technology has been wildly applied for the treatment of wastewater containing dyes and other organic pollutants. However, biologically treatment should be further applied after heterogeneous electro-Fenton process in order get better effluent quality. In the present study, a simple electropolymerization method using poly (3,4-ethylenedioxythiophene) (PEDOT) and graphene oxide (GO) was applied for graphite felt (GF) electrode modification as cathode in EF system, and coupling subsequently aerobic granular sludge (AGS) biological treatment for dye wastewater treatment. The modified electrode was characterized by scanning electron microscopy (SEM), Raman spectrum, and cyclic voltammetry (CV). Data implied that much higher H2O2 productivity, current response and coulomb efficiency (CE) were achieved by using GO/PEDOT:NaPSS modified GF. The results could be ascribed to the synergistic effect between PEDOT and GO that accelerated the electron transfer rate. Moreover, the H2O2 production capacity remained over 84.2% after 10-times reuses for GO/PEDOT:NaPSS modified GF, indicating that GO significantly improved the stability and life of electrode. Compared with the single system, the total organic carbon (TOC) and chemical oxygen demand (COD) removal efficiencies of the combined system degradation methylene blue (MB) wastewater were significantly improved. Therefore, this modified GF could be used as a potentially useful cathode in heterogeneous EF technology for actual wastewater treatment and the combined system have a promising engineering application value in MB wastewater degradation field.


Asunto(s)
Colorantes/química , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/química , Análisis de la Demanda Biológica de Oxígeno , Compuestos Bicíclicos Heterocíclicos con Puentes , Electrodos , Grafito , Peróxido de Hidrógeno , Azul de Metileno , Polímeros , Aguas del Alcantarillado , Aguas Residuales/química
4.
Invest Ophthalmol Vis Sci ; 60(13): 4378-4387, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31634395

RESUMEN

Purpose: Iron supplementation therapy is used for iron-deficiency anemia but has been associated with macular degeneration in a 43-year-old patient. Iron entry into the neurosensory retina (NSR) can be toxic. It is important to determine conditions under which serum iron might cross the blood retinal barrier (BRB) into the NSR. Herein, an established mouse model of systemic iron overload using high-dose intraperitoneal iron dextran (IP FeDex) was studied. In addition, because the NSR expresses the iron regulatory hormone hepcidin, which could limit iron influx into the NSR, we gave retina-specific hepcidin knockout (RS-HepcKO) mice IP FeDex to test this possibility. Methods: Wild-type (WT) and RS-HepcKO mice were given IP FeDex. In vivo retina imaging was performed. Blood and tissues were analyzed for iron levels. Quantitative PCR was used to measure levels of mRNAs encoding iron regulatory and photoreceptor-specific genes. Ferritin and albumin were localized in the retina by immunofluorescence. Results: IP FeDex in both WT and RS-HepcKO mice induced high levels of iron in the liver, serum, retinal vascular endothelial cells (rVECs), and RPE, but not the NSR. The BRB remained intact. Retinal degeneration did not occur. Conclusions: Following injection of high-dose IP FeDex, iron accumulated in the BRB, but not the NSR. Thus, the BRB can shield the NSR from iron delivered in this manner. This ability is not dependent on NSR hepcidin production.


Asunto(s)
Barrera Hematorretinal/metabolismo , Células Endoteliales/metabolismo , Sobrecarga de Hierro/metabolismo , Complejo Hierro-Dextran/administración & dosificación , Hierro/metabolismo , Vasos Retinianos/metabolismo , Albúminas/metabolismo , Animales , Modelos Animales de Enfermedad , Ferritinas/metabolismo , Técnica del Anticuerpo Fluorescente Indirecta , Hepcidinas/farmacología , Inyecciones Intraperitoneales , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transferrina/metabolismo
5.
Bioresour Technol ; 288: 121504, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31128539

RESUMEN

In the present study, the feasibility of treating high ammonia wastewater was evaluated in a combination of aerobic granular sludge nitrification reactor (AGS-SBR) and poly(butylene succinate) solid denitrification reactor (PBS-SBR). After 90 days operation, the effluent NH4+-N and total nitrogen (TN) removal efficiencies were high of 99.6% and 99.7%, respectively. According to typical cycle, N2O emission rate in AGS nitrification process was much higher than PBS denitrification process. It was found from EEM-PARAFAC that the fluorescence intensity scores (protein-like and humic like substances) of soluble microbial products (SMP) in AGS-SBR were the significant higher than in PBS-SBR. Microbial community analysis showed that Thauera was main genus in AGS-SBR and Hydrogenophaga Simplicispira and Thiomonas were dominant genus in PBS-SBR. The obtained result implied that the combined technology is feasible to remove nitrogen compounds from wastewater to meet the stringent emission standards.


Asunto(s)
Desnitrificación , Aguas del Alcantarillado , Reactores Biológicos , Nitrificación , Nitrógeno
6.
J Pediatr Surg ; 52(9): 1409-1415, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28535960

RESUMEN

PURPOSE: Appendectomy has remained the gold standard treatment of acute appendicitis for more than 100years. Nonoperative management (NOM) has been shown to be a valid treatment alternative for acute uncomplicated appendicitis in adults. A systematic review of available evidence comparing operative management (OM) and NOM in children with acute uncomplicated appendicitis was performed. METHODS: Systematic searches of MedLine, Embase, and a clinical trial register (https://clinicaltrials.gov/) were performed in March 2016. Only articles that studied NOM for uncomplicated appendicitis in children were included. Data generation was performed independently by two authors, and quality was assessed using the rating schema by the Oxford Centre for Evidence-Based Medicine. RESULTS: 15 articles were selected: four retrospective analyses, four prospective cohort studies, four prospective nonrandomized comparative trials and one randomized controlled trial (RCT). Initial success of the NOM groups (a cure within two weeks of intervention) ranged from 58 to 100%, with 0.1-31.8% recurrence at one year. CONCLUSION: Although present literature is scarce, publications support the feasibility of further studies investigating NOM of acute uncomplicated appendicitis in children. Higher quality prospective RCTs with larger sample sizes and robust randomization methods, studying the noninferiority of NOM with antibiotics compared with OM are required to establish its utility. LEVEL OF EVIDENCE: This manuscript is a systematic review and thus assigned the lowest evidence used from the manuscripts analyzed which is a Level IV.


Asunto(s)
Antibacterianos/uso terapéutico , Apendicitis/tratamiento farmacológico , Enfermedad Aguda , Niño , Femenino , Humanos , Tiempo de Internación , Calidad de Vida , Recurrencia , Resultado del Tratamiento
7.
ANZ J Surg ; 87(10): 780-783, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27581039

RESUMEN

BACKGROUND: Pull-through of ganglionic bowel is essential for successful treatment of Hirschsprung's disease. We studied the incidence of transition zone pull-through in our institution and compared its outcome with ganglionic bowel pull-through. METHODS: Children who underwent Soave's pull-through for Hirschsprung's disease from January 2005 to November 2012 were studied. Patients were divided into two groups: ganglionic bowel pull-throughs (Group 1) and transition zone pull-throughs (Group 2). Demographics, presentations, surgical procedure, post-operative results and complications including redo procedures were recorded and reviewed along with histopathology reports. RESULTS: Fifty patients underwent Soave's pull-through for Hirschsprung's disease in our group. The median age at surgery was 13.5 days in Group 1 and 22.5 days in Group 2. Transition zone pull-through occurred in eight children (16%). Transition zone pull-through was attributed to errors in histologic interpretation (n = 5), sampling (n = 2) and surgical technique (n = 1). The transition zone was significantly longer in Group 2 (P = 0.002). Constipation and enterocolitis were the main complications needing therapy. One child in Group 2 required surgery for adhesive intestinal obstruction. CONCLUSIONS: The length of the transition zone in children with transition zone pull-through was significantly longer. Though our children with transition zone pull-through did not require redo surgery the possibility of redo surgery remains. Transition zone pull-through should still be considered an error and should be prevented.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Enfermedad de Hirschsprung/patología , Enfermedad de Hirschsprung/cirugía , Errores Médicos/prevención & control , Recto/cirugía , Estreñimiento/epidemiología , Estreñimiento/etiología , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Enterocolitis/epidemiología , Enterocolitis/etiología , Femenino , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/epidemiología , Humanos , Incidencia , Recién Nacido , Obstrucción Intestinal/epidemiología , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Masculino , Complicaciones Posoperatorias/etiología , Recto/inervación , Recto/patología , Reoperación/estadística & datos numéricos , Centros de Atención Terciaria , Resultado del Tratamiento
8.
BMJ Open ; 6(12): e013299, 2016 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-28003294

RESUMEN

INTRODUCTION: This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. DESIGN: A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. PARTICIPANTS: Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. INTERVENTIONS: Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. ANALYSIS: Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. ETHICS AND DISSEMINATION: The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. TRIAL REGISTRATION NUMBERS: NCT02795793; ACTRN12616000788471.


Asunto(s)
Antibacterianos/uso terapéutico , Apendicectomía , Apendicitis/tratamiento farmacológico , Tratamiento Conservador , Enfermedad Aguda , Adolescente , Apendicitis/cirugía , Australia , Niño , Análisis Costo-Beneficio , Manejo de la Enfermedad , Femenino , Humanos , Tiempo de Internación , Masculino , Estudios Prospectivos , Proyectos de Investigación , Resultado del Tratamiento
9.
Front Plant Sci ; 7: 931, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27458463

RESUMEN

Saline-alkaline stress, caused by high levels of harmful carbonate salts and high soil pH, is a major abiotic stress that affects crop productivity. Alfalfa is a widely cultivated perennial forage legume with some tolerance to biotic and abiotic stresses, especially to saline-alkaline stress. To elucidate the mechanism underlying plant saline-alkaline tolerance, we conducted transcriptome analysis of whole alfalfa seedlings treated with saline-alkaline solutions for 0 day (control), 1 day (short-term treatment), and 7 days (long-term treatment) using ion torrent sequencing technology. A transcriptome database dataset of 53,853 unigenes was generated, and 2,286 and 2,233 genes were differentially expressed in the short-term and long-term treatment, respectively. Gene ontology analysis revealed 14 highly enriched pathways and demonstrated the differential response of metabolic pathways between the short-term and long-term treatment. The expression levels of 109 and 96 transcription factors were significantly altered significantly after 1 day and 7 days of treatment, respectively. Specific responses of peroxidase, flavonoids, and the light pathway component indicated that the antioxidant capacity was one of the central mechanisms of saline-alkaline stress tolerance response in alfalfa. Among the 18 differentially expressed genes examined by real time PCR, the expression levels of eight genes, including inositol transporter, DNA binding protein, raffinose synthase, ferritin, aldo/keto reductase, glutathione S-transferase, xyloglucan endotrans glucosylase, and a NAC transcription factor, exhibited different patterns in response to saline and alkaline stress. The expression levels of the NAC transcription factor and glutathione S-transferase were altered significantly under saline stress and saline-alkaline stress; they were upregulated under saline-alkaline stress and downregulated under salt stress. Physiology assays showed an increased concentration of reactive oxygen species and malondialdehyde and a decreased content of chlorophyll, indicating that anti-oxidation and detoxification play an important role in response to saline-alkaline stress. Overall, the transcriptome analysis provided novel insights into the saline-alkaline stress tolerance response mechanisms in alfalfa.

10.
Bioorg Med Chem Lett ; 22(22): 6882-7, 2012 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23044370

RESUMEN

A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, (1)H NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Preliminary research on the mechanism of action showed that the inhibition might perform through combination of apoptosis, autophagy and cell cycle arrest.


Asunto(s)
Antineoplásicos/síntesis química , Pirazoles/química , Pirazoles/síntesis química , Serina/análogos & derivados , Antineoplásicos/química , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Ácidos Carboxílicos/química , Línea Celular Tumoral , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Peptidomiméticos , Pirazoles/toxicidad , Serina/síntesis química , Serina/química , Serina/toxicidad , Relación Estructura-Actividad
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 81(1): 372-9, 2011 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-21733750

RESUMEN

A series of fluorescent compounds, containing pyrazolo[1,5-a]pyrazin-4(5H)-one moiety, were designed and synthesized from ethyl 1-(2-oxo-2-phenylethyl)-3-phenyl-1H-pyrazole-5-carboxylates. The structures of the compounds have been confirmed by IR, (1)H NMR, HRMS and X-ray crystal diffraction. The optical properties of the compounds were investigated by UV-vis absorption and fluorescence spectroscopy. The effect of pH on the UV-vis absorption of compound 2a in methanol-H(2)O solutions was studied and interpreted by theory calculation. The pK(a) value of compound 2a was determined by the absorption spectra.


Asunto(s)
Pirazinas/química , Pirazoles/química , Piridinas/química , Piridinas/síntesis química , Cristalografía por Rayos X , Modelos Biológicos , Modelos Moleculares , Simulación de Dinámica Molecular , Estructura Molecular , Pirazinas/síntesis química , Pirazoles/síntesis química , Espectrometría de Fluorescencia/métodos
12.
Bioorg Med Chem Lett ; 20(16): 4766-70, 2010 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-20637610

RESUMEN

A series of novel oxime-containing pyrazole derivatives were synthesized by the reaction of ethyl 3-phenyl-1H-pyrazole-5-carboxylate derivatives and 2-bromo-1-phenylethanone followed by the reaction with hydroxylamine hydrochloride. The structures were determined by IR, (1)H NMR, HRMS, and X-ray analysis. A dose- and time-dependent inhibition of proliferation was observed in A549 lung cancer cell after compound treatment. Inhibition of growth was mainly attributed to the autophagy induction.


Asunto(s)
Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Oximas/química , Pirazoles/química , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cristalografía por Rayos X , Evaluación Preclínica de Medicamentos , Humanos , Neoplasias Pulmonares/patología , Conformación Molecular , Pirazoles/síntesis química , Pirazoles/uso terapéutico , Relación Estructura-Actividad
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