•Optimized dorzolaminde HCl chitosan nanoparticles were dispersed in alginate gel.•In vitro release from optimized in situ gel nanoparticle formulation C2S4 showed sustained release.•Ex vivo ...permeation study proved in situ gel nanoparticle as better formulation for treatment of glaucoma as compared to marketed solution.•More retention in the corneal region and hence better patient compliance.
The most important risk associated with glaucoma is the onset and progression of intraocular pressure. The objective of this study was to formulate in situ gel of chitosan nanoparticles to enhance the bioavailability and efficacy of dorzolamide in the glaucoma treatment. Optimized nanoparticles were spherical in shape (particle size: 164nm) with a loading efficiency of 98.1%. The ex vivo release of the optimized in situ gel nanoparticle formulation showed a sustained drug release as compared to marketed formulation. The gamma scintigraphic study of prepared in situ nanoparticle gel showed good corneal retention compared to marketed formulation. HET-CAM assay of the prepared formulation scored 0.33 in 5min which indicates the non-irritant property of the formulation. Thus in situ gel of dorzolamide hydrochloride loaded nanoparticles offers a more intensive treatment of glaucoma and a better patient compliance as it requires fewer applications per day compared to conventional eye drops.
Insulin secretion is initiated by activation of voltage-gated Ca
channels (VGCC) to trigger Ca
-mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell ...membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (I
) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated I
and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling. SWELL1 depletion in MIN6 cells and islets significantly impairs glucose-stimulated insulin secretion. Tamoxifen-inducible β-cell-targeted Swell1 KO mice have normal fasting serum glucose and insulin levels but impaired glucose-stimulated insulin secretion and glucose tolerance; and this is further exacerbated in mild obesity. Our results reveal that β-cell SWELL1 modulates insulin secretion and systemic glycaemia by linking glucose-mediated β-cell swelling to membrane depolarization and activation of VGCC-triggered calcium signaling.
This paper examines the effects of return spillovers from regional (Saudi Arabia) and global (US) markets to GCC stock markets (Bahrain, Oman, Kuwait, Qatar, United Arab Emirates). The paper develops ...various bivariate GARCH models for regional and global returns: BEKK, constant correlation and dynamic correlation. The specification tests are used to choose between the models with and without asymmetric effects. The estimated innovations for the regional and global returns are then used as input for the univariate volatility spillover model which allows the unexpected returns of any particular GCC stock market to be driven by three sources of shocks: local, regional from Saudi Arabia and global from US. We find significant return spillover effects from Saudi Arabia and US to GCC markets. Trade, turnover and institutional quality have significant impacts on regional volatility spillovers from Saudi Arabia to GCC markets. There are macroeconomic policy implications associated with the strengthening of intra-regional and cross-border trade in goods, services and assets and regulatory framework.
•Paper examines the effects of return spillovers from regional (Saudi Arabia) and global (US) markets to GCC stock markets.•Paper develops various bivariate GARCH models: BEKK, constant correlation and dynamic correlation.•We find significant return spillover effects from Saudi Arabia and US to GCC markets.•There are macroeconomic policy implications associated with the strengthening of intra-regional and cross-border trade.
Mechanism of eosinophilic esophagitis Mishra, Anil
Immunology and allergy clinics of North America,
02/2009, Letnik:
29, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Eosinophilic esophagitis (EoE) is a newly recognized disease and is an emerging entity throughout developing and developed countries, including the United States. Therefore, understanding the causes, ...natural history, diagnosis, and management is important for future therapeutic interventions. The pathogenesis of EoE is still not clear, but a growing body of evidence has established that this condition represents a T-cell-mediated immune response involving several proinflammatory mediators and chemoattractants known to regulate eosinophilic accumulation in the esophagus, such as IL-4, IL-5, IL-3 and eotaxin-1, -2, and -3. Determining the mechanism or mechanisms through which human esophageal-derived factors ultimately induce the functional abnormalities observed, and to which antigens patients who have EoE are sensitized that lead to the manifestation of symptoms, is of significant interest.
The pharmacologically characterized receptor subtype of the serotonin family, the 5HT1A receptor is implicated in the pathophysiology and treatment of depression and anxiety-related disorders. Being ...the most extensively targeted receptor for developing novel antidepressants and anxiolytics, a near-ideal theoretical model can aid in high-throughput screening of promising drug candidates. However, the design of potential drug candidates suffers owing to a lack of complete structural information. In this work, homology models of 5-HT1A receptor are generated using two distinct alignments (CW and PSTA) and model building methods (KB and EB). The developed models are validated for virtual screening using a ligand dataset of agonists and antagonists. The best-suited model was efficient in discriminating agonist/antagonist binding. Correlation plots between pKi and docking (R
≥ 0.6, R
≥ 0.7) and MM-GBSA dG bind values (R
≥ 0.5, R
≥ 0.7) revealed optimum corroboration between in vitro and in silico outcomes, which further suggested the usefulness of the developed model for the design of high-affinity probes for the neurological disorders.Communicated by Ramaswamy H. Sarma.
Determinants of FDI inflows to Arab economies Aziz, Omar G.; Mishra, Anil V.
The journal of international trade & economic development,
04/2016, Letnik:
25, Številka:
3
Journal Article
Recenzirano
The paper studies location determinants of foreign direct investment (FDI) to 16 Arab economies over the period from 1984 to 2012, by employing Arellano-Bover/Blundell-Bond linear dynamic panel data ...estimation. We find that market size, trade openness, preferential trade agreements and financial development have significant positive impact on FDI inflows to Arab economies. FDI in Arab economies appears to be resource seeking since the total oil supply variable is positive and significant. The paper finds that better institutions and educated labour force may play a key role in attracting FDI inflows. We suggest that Arab economies should sequence their economic policy measures with the institutional ones, beginning with a focus on privatization and trade liberalization, and subsequently shift to improvement in economic growth.
The successful ophthalmic delivery system is reliant on the diminution in the precorneal loss of drugs by increasing the corneal contact time and increasing the transcorneal permeability, which may ...enhance the bioavailability of drug to the eyes. The objective of this investigation was to develop and evaluate the potential of microemulsions of gatifloxacin with respect to the conventional eye drops of gatifloxacin. Oil-in-water microemulsions were prepared with different concentrations of oil, surfactant and co-surfactant using aqueous titration method. All formulations showed circular shape droplets, displayed an average droplet size ranged between 51 and 74 nm and absolute zeta potential values ranged from 15 to 24 mV, with optimum physicochemical characteristics suitable for eye. The optimized microemulsion possessed good stability, showed greater adherence to corneal surface and good permeation of gatifloxacin in the anterior chamber of the eye, resulting in a twofold increase in gatifloxacin concentration than the conventional dosage form. Hence, the optimized microemulsions showed increased intraocular penetration and enhance ocular bioavailability of gatifloxacin.
This literature review explores the existing work and practices in applying thematic analysis natural language processing techniques to financial data in cloud environments. This work aims to improve ...two of the five Vs of the big data system. We used the PRISMA approach (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) for the review. We analyzed the research papers published over the last 10 years about the topic in question using a keyword-based search and bibliometric analysis. The systematic literature review was conducted in multiple phases, and filters were applied to exclude papers based on the title and abstract initially, then based on the methodology/conclusion, and, finally, after reading the full text. The remaining papers were then considered and are discussed here. We found that automated data discovery methods can be augmented by applying an NLP-based thematic analysis on the financial data in cloud environments. This can help identify the correct classification/categorization and measure data quality for a sentiment analysis.
We examine the effect of ownership structure on firm performance, for firms listed on Vietnamese stock exchanges, using 2744 firm‐year observations over the period from 2007 to 2012. We find a ...non‐linear relationship between ownership structure and firm performance. State ownership has a convex relationship with firm performance. This paper finds that firm performance increases beyond 28.67 percent level of state ownership. Foreign ownership has a concave relationship with firm performance. We find that firm performance increases with an increase of foreign ownership up to a level of 43 percent and then decreases. Policy makers should encourage foreign ownership and widely dispersed state ownership in firms, which can help improve firm performance.
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