Intermittent hypoxia-induced endothelial activation in EA.hy926 cells in vitro

INTRODUCTION: Obstructive sleep apnoea is characterised by repetitive episodes of complete or partial upper airway collapse during sleep, leading to recurrent drop in arterial oxygenation (intermittent hypoxia [IH]) and sleep fragmentation. Repetitive IH with rapid reversal to normoxia initiates a series of pathological events such as oxidative stress, inflammation, and sympathetic activation, all of which contributes to endothelial dysfunction (a predictor and precursor of atherosclerosis). The aim of the current study was to investigate the effect of IH on the activation of endothelial cells in a cellular model in …published_or_final_versio

WiseNews database for upper primary students and teachers

Parallel Session 8 - 8.02 PaperElectronic databases are widely used by students and teachers at secondary and tertiary level to gather information for academic purposes. Few studies have investigated their use in primary education, especially in the Asian context. A pilot study conducted a year ago has shown that WiseNews, an electronic news database, was effective in facilitating the inquiry project-based learning of primary students at a school in Hong Kong. The current research extends the pilot study by examining the use of WiseNews by upper primary students and their teachers in five local primary schools. Automatic records of students’ and teachers’ database activities provided by WiseNews will be used to examine the usage habit of students and teachers. Students and teachers will be surveyed regarding their perceived usefulness of WiseNews database for learning and teaching purposes. Data collection and analysis adopted a mixed method design. The qualitative analysis will include an in-depth analysis of the types of articles retrieved by the students, in addition to the responses to the open-ended questions on the survey. This research will help teachers and school administrators to assess the effectiveness of WiseNews database in facilitating learning at upper primary levels.postprintThe International Conference on Primary Education, The Hong Kong Institute of Education, Hong Kong, China, 25-27 November 2009

Intermittent hypoxia accelerates adipogenic differentiation in human subcutaneous preadipocytes in vitro

Poster Discussion Session - B30. Beast is Inside: What Causes the Adverse Outcomes of Sleep Disordered Breathing: no. A2704RATIONALE: Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is highly associated with obesity. Depot-specific adipogenic differentiation, an important physiological mechanism in maintaining adipose tissue homeostasis, could be regulated by intracellular transcriptional factors, extracellular signaling pathways and inflammation in obesity. However, the impact of IH on adipogeneisis is unclear. This study aims at investigating the pathologic role of IH during the adipogenic differentiation process in human subcutaneous preadipocytes in …published_or_final_versio

An electronic news database for upper primary school students and teachers in Hong Kong

The current research extended the pilot study and examined the use of an electronic news database by upper primary school students and their teachers in five local schools in Hong Kong. We used a mixed-methods design for data collection and analysis. We examined records of users' database activities for the usage patterns of students and teachers. Surveys and phone interviews were conducted to assess their perceptions of the usefulness of the electronic database for learning and teaching. The Revised Two-Factor Learning Process Questionnaire (R-LPQ-2F) was employed to assess students' learning approaches and their associations with news database use, and perceptions were examined. Findings revealed that younger students tended exclusively to browse, while older students and teachers used both browsing and keyword searching. Use patterns also confirmed that the news database provided accessibility to a vast amount of information. Both students and teachers perceived the electronic database to be useful for learning and teaching. Finally, we found that a deep learning approach was associated with frequency of use and positive perceptions of the usefulness of the electronic database. These results provide potentially important implications for teachers, school administrators, and system designers in developing an efficient electronic database to facilitate learning at upper primary school levels. © American Library Association.link_to_subscribed_fulltex

Intraocular cytokines in neovascular age-related macular degeneration non-responder to ranibizumab treatment

Purpose : To evaluate cytokines level in aqueous humor of ranibizumab (RN) non-responders with neovascular AMD (nAMD) who were treated with either combination of ranibizumab (RN), and photodynamic therapy (PDT) or aflibercept (AF) and explore the prediction cytokines for RN non-responders Methods : This prospective study collected aqueous specimen prospectively from RN non-responder receiving either AF or combination PDT (Study gr.) and RN responders patients (Control gr.) for cytokine analysis at baseline, month 1, 2 and 3 visit of treatment. Cytokines level and changes in 3 treatment groups were compared by using GLMM. Weighted propensity score was used to adjusted for covariate. VEGF, PDGF,PLGF and others angiogenesis/inflammatory cytokines were analyzed by Bio-Plex® Multiplex Immunoassays. Results : Eleven, 8 and 13 eyes received AF treatment, combined PDT, and control respectively. Mean change of visual acuity from baseline is improved [WC1] in the control gr. (P<0.05) while study gr. didn’t show significant changes. In PDT group, 75% of patients showed stabilization or improvement in AMD clinical activity while PLGF, PDGF and leptin level are significant increase at first month: At 2 months visit, VEGF-A level is increase while Endoglin and HB-EGF decline when compare to baseline. At 3 months visit, VEGF-C and HGF concentration are higher in AF group than control group (p=0.02 and 0.02). There are no different in PLGF,PDGF,VEGF-A levels between each treatment group in all visit. PLGF level was higher in study gr. while IL-7 was lower in study gr. (P=0.02 and 0.04 respectively). The combination level of Angiopoetin 2, IL-6, ICAM, Follistatin and IL-3 can predict the response of RN treatment with 83% sensitivity and 72% specificity. Conclusions : Switching to AF may not reduce major cytokines level but resulted in improvement of visual acuity. Combination of PDT and RN resulted increase angiogenesis cytokines. The lack of IL-7 was found in non-responder patient. Apart from cytokine levels, other factors such as cytokine receptors and immune system activity may play a role in non-response patient

Neovascular age-related macular degeneration: intraocular inflammatory cytokines in the poor responder to ranibizumab treatment

Pear Pongsachareonnont,1,2 Michael Ying Kit Mak,2 Cameron Paul Hurst,3 Wai-Ching Lam2,4 1Vitreo-Retinal Research Unit, Department of Ophthamology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; 2Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine, Toronto, ON, Canada; 3Biostatistics Center, Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Department of Ophthalmology, University of Hong Kong, Hong Kong, China Purpose: To determine the levels of interleukin (IL)-6, vascular endothelial growth factor-A, platelet-derived growth factor, placental growth factor (PLGF), and other cytokines in the aqueous fluid of patients with neovascular age-related macular degeneration who respond poorly to ranibizumab. Patients and methods: This is an observational, prospective study. Thirty-two eyes from 30 patients were included in the study: 11 patients who responded poorly to ranibizumab and were switched to aflibercept (AF group), 8 patients who received ranibizumab and photodynamic therapy (PDT group), and 13 patients who responded to ranibizumab (control group). Aqueous fluid samples were collected for analysis of cytokine levels at baseline and after 1, 2, and 3 months of treatment. The effect of treatment on cytokine levels was compared between the study groups and between different time points using a linear mixed-effect regression model. Results: In the AF group, there was an increase in vascular endothelial growth factor-C, IL-7, and angiopoeitin-2 levels (P=0.01) and a decrease in intercellular adhesion molecule and IL-17 levels (P=0.01) between baseline and 3 months. After adjustment for age, sex, race, and type of lesion at baseline, the PLGF level was higher (P=0.02) and the IL-7 level was lower (P=0.04) in the ranibizumab non-responder group than in the ranibizumab responder group. Conclusion: Switching from ranibizumab to aflibercept did not reduce intraocular levels of angiogenesis cytokines, but resulted in improvement of central subfield thickness. PLGF levels were higher in poor responders to ranibizumab. The response of lesions to medication might be related to the stage of choroidal neovascularization. Trial registration: www.ClinicalTrial.gov (NCT02218177c). Keywords: neovascular age-related macular degeneration, choroidal neovascularization, anti-VEGF non-responder, poor responder, ranibizumab and AM

The role of visfatin in intermittent hypoxia-induced inflammation and endothelial dysfunction

Poster Session: A109 - The Impact of Sleep Disordered Breathing on the Heart and other Organ Systems: no. A2409RATIONALE: Intermittent hypoxia (IH), a hallmark feature in obstructive sleep apnea (OSA) associated with transient cessation of breathing during sleep, may be the main culprit underlying endothelial dysfunction, a risk factor for atherosclerosis. Visfatin is a multifaceted adipokine, the extracellular form of which can exert various effects on the vascular endothelium including inflammation, proliferation and endothelium-dependent relaxation. However, little is known about the role of visfatin in inflammation and endothelial dysfunction induced by IH. This study is aimed to compare the effects of visfatin on inflammation and endothelial function between IH and normoxia in endothelial cells. METHODS: IH exposure was performed in the hypoxic chamber in which O2 levels were alternated between 1% for 10 min and 21% for 5 min in one complete cycle and CO2 levels were maintained at 5%. Intermittent normoxia (IN;21% O2 and 5% CO2) exposure was carried out simultaneously in control cell cultures. Endothelial EA.hy926 cells were exposed to IN or IH for 96 cycles with two concentrations of visfatin (10ng/ml and 100ng/ml). Supernatants were collected after treatment to measure the levels of inflammatory markers, interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1, using commercial ELISA kits. Cellular proteins were extracted to determine the expression ofa key enzyme regulating endothelial function, nitric oxide synthase (eNOS) and its activity in terms of phosphorylation at ser1177 [p-eNOS (Ser1177)] using Western blot. RESULTS: IH exposure induced elevation of IL-8 and MCP-1 levels (p<0.05). Visfatin attenuated IH-induced elevation of IL-8 and MCP-1 levels in a dose-dependent manner. Visfatin alone had no effects on basal levels of IL-8 and MCP-1. Western blot analysis revealed that IH exposure significantly suppressed p-eNOS expression but not eNOS expression in EA.hy926 cells. In the presence of visfatin, no differences were found in the basal expression of p-eNOS and eNOS or in IH-induced suppression of p-eNOS. CONCLUSION: These results provided evidence that visfatin might play a pivotal role in IH-induced endothelial inflammation but not in reversing endothelial dysfunction in OSA.link_to_OA_fulltex

Low-intensity intermittent hypoxia promotes subcutaneous adipogenic differentiation

Poster presentationIntroduction: Obstructive sleep apnoea (OSA), characterised by intermittent hypoxia (IH), is highly associated with obesity. Depot-specific adipogenic differentiation, an important physiological mechanism in maintaining adipose tissue homeostasis, could be regulated by intracellular transcriptional factors, extracellular signalling pathways, and inflammation. However, the impact of IH on adipogenesis is unclear. This study aimed to investigate the role of IH in adipogenic differentiation in vivo and in vitro. Methods: The Sprague Dawley rats were subjected to intermittent normoxia (IN) or IH (each cycle: 240 seconds for 10% O2 and 120 seconds for 21% O2) for 6 weeks. Human subcutaneous preadipocytes (HPAs) underwent six differentiation cycles into mature adipocytes. Each differentiation cycle consisted of two sequential procedures of differentiation (for 3 days) and maintenance (for 2 days). During each 3-day differentiation, HPAs were subjected to IH (IH; 1% for 10 min and 21% O2 for 5 min per cycle; 5% CO2) or IN treatment. The degree of adipogenic differentiation was evaluated by the measurements of adipogenic transcriptional factors (CEBPα, PPARγ CEBPδ, and CHOP) and adipocyte-specific proteins (FABP4 and GLUT4) using Q-PCR and/or Western blots. The production of oily droplets in HPAs was detected by Oil Red O staining. The analysis of insulin-like growth factor 1 receptor (IGF-1R)/Akt pathway in HPAs was achieved by incubation of IGF-1R selective kinase inhibitor NVP-AEW541 (0.1 μmol/L) using Western blots. ELISA was applied to detect adiponectin in tissue-conditioned media and pro-inflammatory markers (interleukin [IL]-6 and monocyte chemoattractant protein [MCP]-1) in HPAs-conditioned media. Results: The up-regulation of pro-adipogenic markers (CEBPα, PPARγ, FABP4) and down-regulation of antiadipogenic markers CHOP were found in IH-exposed subcutaneous adipose tissue (SAT) but not visceral adipose tissue (VAT). In addition, IH exposure facilitated the release of adiponectin in SAT- but not VATconditioned media. In line with in-vivo results, IH accelerated the accumulation of oil droplets in HPAs. During differentiation, IH caused elevation of adipogenesis-associated markers (FABP4, GLUT4, CEBPα, andPPARγ) compared to cells exposed to IN. Moreover, the reduction in expression of CEBPδ was prevented by IH exposure with adipogenic development of HPAs. The pro-adipogenic role of IGF-1R/Akt activation in IHexposed HPAs was significantly attenuated by IGF-1R kinase inhibitor NVP-AEW541. In addition, IH also induced elevated levels of IL-6 and MCP-1 in the conditioned media during the process of HPAs differentiation. Conclusion: Low-frequency IH exposure could promote the adipogenic differentiation of SAT and subcutaneous preadipocytes (HPAs) via regulating transcriptional factors, IGF-1/Akt signalling pathway and inflammation