Role of epac in the pathogenesis of ischemic stroke

Poster Presentations: Theme 2published_or_final_version15th Research Postgraduate Symposium, Hong Kong, China, 1-2 December 2010. In Abstract - Poste Presentations (Theme II) of 15th Research Postgraduate Symposium, 2010, p. 8

Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy

Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions. To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion (tMCAO) was performed on Epac1-deficient (Epac1) mice, Epac2-deficient (Epac2) mice, and their wild type counterparts (Epac1+/+ and Epac2+/+). Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neuronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 (AQP4), glial fibrillary acidic protein (GFAP), peroxiredoxin 6 (Prx6) were observed in ipsilateral retinae. Epac2 ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2+/+. However, Epac1 ipsilateral retinae displayed similar pathology as those in Epac1+/+ mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.published_or_final_versio

Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity

published_or_final_versio

Adiponectin is protective against oxidative stress-induced cytotoxicity in amyloid-beta neurotoxicity

Oral PresentationBeta-amyloid (Aβ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation, and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation, and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes mellitus (T2DM) which is characterised by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adipon…published_or_final_versio

Cognitive impairment in adiponectin-knockout mice

Oral Presentationpublished_or_final_versio

Qualitative characterization of healthcare wastes

The biological hazard inherent in the clinical wastes should be considered during the management and treatment process as well as the disposal into the environment. In this chapter, the risks associated with the clinical wastes as well as the management of these wastes are discussed. The chapter focused on reviewing the types of healthcare wastes generated from hospitals and clinics as well as the regulations and management practices used for these wastes. Moreover, the health risk associated with the infectious agents which have the potential to be transmitted into the environment. It has appeared that the clinical wastes represent real hazards for the human health and the environment if they were not managed properly

Restoration of Liquid Effluent from Oil Palm Agroindustry in Malaysia using UV/TiO2 and UV/ZnO Photocatalytic Systems: A Comparative Study

In this study, we have employed a photocatalytic method to restore the liquid effluent from a palm oil mill in Malaysia. Specifically, the performance of both TiO2 and ZnO was compared for the photocatalytic polishing of palm oil mill effluent (POME). The ZnO photocatalyst has irregular shape, bigger in particle size but smaller BET specific surface area (9.71 m2/g) compared to the spherical TiO2 photocatalysts (11.34 m2/g). Both scavenging study and post-reaction FTIR analysis suggest that the degradation of organic pollutant in the TiO2 system has occurred in the bulk solution. In contrast, it is necessary for organic pollutant to adsorb onto the surface of ZnO photocatalyst, before the degradation took place. In addition, the reactivity of both photocatalysts differed in terms of mechanisms, photocatalyst loading and also the density of photocatalysts. From the stability test, TiO2 was found to offer higher stability, as no significant deterioration in activity was observed after three consecutive cycles. On the other hand, ZnO lost around 30% of its activity after the 1st-cycle of photoreaction. The pH studies showed that acidic environment did not improve the photocatalytic degradation of the POME, whilst in the basic environment, the reaction media became cloudy. In addition, longevity study also showed that the TiO2 was a better photocatalyst compared to the ZnO (74.12%), with more than 80.0% organic removal after 22 h of UV irradiation

Growth suppressive effect of pegylated arginase in malignant pleural mesothelioma xenografts

BACKGROUND: Malignant pleural mesothelioma (MPM) is a difficult-to-treat global disease. Pegylated arginase (BCT-100) has recently shown anti-tumor effects in hepatocellular carcinoma, acute myeloid leukemia and melanoma. This study aims to investigate the effects of PEG-BCT-100 in MPM. METHODS: A panel of 5 mesothelioma cell lines (H28, 211H, H226, H2052 and H2452) was used to study the in vitro effects of BCT-100 by crystal violet staining. The in vivo effects of BCT-100 were studied using 211H and H226 nude mice xenografts. Protein expression (argininosuccinate synthetase, ornithine transcarbamylase, cleaved PARP, cleaved caspase 3, cyclins (A2, D3, E1 and H), CDK4 and Ki67) and arginine concentration were evaluated by Western blot and ELISA respectively. Cellular localization of BCT-100 was detected by immunohistochemistry and immunoflorescence. TUNEL assay was used to identify cellular apoptotic events. RESULTS: Argininosuccinate synthetase was expressed in H28, H226, and H2452 cells as well as 211H and H266 xenografts. Ornithine transcarbamylase was undetectable in all cell lines and xenograft models. BCT-100 reduced in vitro cell viability (IC50 values at 13-24 mU/ml, 72 h) across different cell lines and suppressed tumor growth in both 211H and H226 xenograft models. BCT-100 (60 mg/kg) significantly suppressed tumor growth (p < 0.01) with prolonged median survival (p < 0.01) in both xenograft models. Combining BCT-100 with pemetrexed or cisplatin conferred no additional benefits over single agents. Serum and intratumoral arginine levels were effectively decreased by BCT-100, associated with cytosolic accumulation of BCT-100 within tumor cells. Apoptosis (PARP cleavage in 211H xenografts; Bcl-2 downregulation, and cleavage of PARP and caspase 3 in H226 xenografts; positive TUNEL staining in both) and G1 arrest (downregulation of cyclin A2, D3, E1 and CDK4 in 211H xenografts; suppression of cyclin A2, E1, H and CDK4 in H226 xenografts) were evident with BCT-100 treatment. Furthermore, proliferative factor Ki67 was downregulated in BCT-100 treatments arms. CONCLUSIONS: BCT-100 suppressed tumor growth with prolonged median survival partially mediated by intratumoral arginine depletion resulting in apoptosis and G1 arrest in mesothelioma xenograft models. The findings provide scientific evidence to support further clinical development of BCT-100 in treatment of MPM.published_or_final_versio

Carriage niches and molecular epidemiology of Staphylococcus lugdunensis and methicillin-resistant S. lugdunensis among patients undergoing long-term renal replacement therapy

We collected nasal, axilla, and groin swabs from 252 adult patients from 2 nephrology centers in Hong Kong. Staphylococcus lugdunensis carriage was detected in 51.6% patients (groin, 39.3%; axilla, 19.8%; nose, 17.9%). The carriage rates of methicillin-sensitive S. lugdunensis and methicillin-resistant S. lugdunensis (MRSL) were 46.0% and 8.3%, respectively. Independent risk factors for S. lugdunensis carriage included male sex (odds ratio [OR], 4.4), hemodialysis (OR, 2.2), and aged 18–50 years (OR, 2.4). The isolates belonged to 10 pulsotype clusters (n = 129) and 8 singletons (n = 8). All MRSL and most gentamicin- and tetracycline-resistant strains were found in a predominating sequence type 3 clone, designated HKU1, which accounted for 51.8% of all colonizing S. lugdunensis strains. The 21 MRSL isolates had SCCmec type V (n = 18), type IV (n = 2), and type I (n = 1). The finding highlights the potential for dissemination of multidrug resistance through successful S. lugdunensis clones.postprin