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71.
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M. Shanika Fernando A. K. D. V. K. Wimalasiri S. P. Ratnayake J. M. A. R. B. Jayasinghe Gareth R. William D. P. Dissanayake K. M. Nalin de Silva Rohini M. de Silva 《RSC advances》2019,9(61):35588
A novel hydroxyapatite montmorillonite (HAP-MMT) nanocomposite system was synthesized using a simple wet chemical in situ precipitation method. Neat nano hydroxyapatite (HAP) was also synthesized for comparison. The characterization of the materials was carried out using Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), X-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET) isotherms to study the functional groups, morphology, crystallinity and the surface area respectively. Batch adsorption studies and kinetic studies on fluoride adsorption were conducted for the HAP-MMT system and for neat HAP. The effect of parameters such as contact time, pH, initial concentration, temperature, and thermodynamic parameters and the effect of coexisting ions on fluoride adsorption by HAP-MMT were studied. Results of the isotherm experiments were fitted to four adsorption isotherm models namely Langmuir, Freundlich, Temkin and Dubinin Radushkevich. Fluoride adsorption over HAP-MMT fitted to the Freundlich adsorption isotherm model and showed more than two-fold improved adsorption capacity (16.7 mg g−1) compared to neat HAP. The best-fitting kinetic model for both adsorbents was found to be pseudo second order. Calculated thermodynamic parameters indicated that the fluoride adsorption by HAP-MMT is more favorable compared to that on HAP within the temperature range of 27 °C–60 °C. Improved fluoride adsorption by HAP-MMT is attributed to the exfoliated nature of HAP-MMT. Gravity filtration studies carried out using a 1.5 ppm fluoride solution, which is closer to the ground water fluoride concentrations of Chronic Kidney Disease of unknown etiology (CKDu) affected areas in Sri Lanka, resulted in a 1600 ml g−1 break through volume indicating the potential of HAP-MMT to be used in real applications.A novel hydroxyapatite montmorillonite (HAP-MMT) nanocomposite was synthesized using a simple wet chemical in situ precipitation method. This nanocomposite showed improved adsorption properties towards fluoride ions in water. 相似文献
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Stuart A. Morgan Emma L. McCabe Laura L. Gathercole Zaki K. Hassan-Smith Dean P. Larner Iwona J. Bujalska Paul M. Stewart Jeremy W. Tomlinson Gareth G. Lavery 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(24):E2482-E2491
The adverse metabolic effects of prescribed and endogenous glucocorticoid (GC) excess, Cushing syndrome, create a significant health burden. We found that tissue regeneration of GCs by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), rather than circulating delivery, is critical to developing the phenotype of GC excess; 11β-HSD1 KO mice with circulating GC excess are protected from the glucose intolerance, hyperinsulinemia, hepatic steatosis, adiposity, hypertension, myopathy, and dermal atrophy of Cushing syndrome. Whereas liver-specific 11β-HSD1 KO mice developed a full Cushingoid phenotype, adipose-specific 11β-HSD1 KO mice were protected from hepatic steatosis and circulating fatty acid excess. These data challenge our current view of GC action, demonstrating 11β-HSD1, particularly in adipose tissue, is key to the development of the adverse metabolic profile associated with circulating GC excess, offering 11β-HSD1 inhibition as a previously unidentified approach to treat Cushing syndrome.Estimates suggest that 1–2% of the population of the United States and United Kingdom take prescribed glucocorticoids (GCs) for the treatment of a broad spectrum of inflammatory and autoimmune diseases (1, 2). Despite the efficacy of GCs, 70% of patients experience an adverse systemic side-effect profile. The resultant Cushingoid features include central obesity, proximal myoatrophy, hypertension, skin thinning, osteoporosis, hepatic steatosis, insulin resistance, and type 2 diabetes (3, 4). Collectively, this contributes to increased risk of cardiovascular morbidity and mortality (5, 6). These features are replicated in patients with much rarer endogenous GC excess (Cushing syndrome), as first described by Harvey Cushing in 1932 (7). Current medical therapeutic options that reverse the tissue-specific consequences of hypercortisolism are limited.GC availability and action depend not only upon circulating levels but also on tissue-specific intracellular metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). Key metabolic tissues including liver, adipose tissue, and skeletal muscle express 11β-HSD type 1 (11β-HSD1), which coverts inactive cortisone to active cortisol [11-dehydrocorticosterone (11DHC) and corticosterone (CORT) in rodents, respectively] (8). In the setting of GC excess, the relative contribution to the metabolic effects induced by GCs of simple delivery of active GCs (cortisol or CORT) to a target tissue, compared with the regeneration of active GCs by 11β-HSD1 within the tissue, has not been determined.Type 2 11β-HSD (11β-HSD2) is predominately expressed in the kidney, colon, and salivary gland and catalyzes the inactivation of cortisol to cortisone (CORT to 11DHC in rodents). This not only protects the mineralocorticoid receptor from occupancy by cortisol but also crucially provides substrate for 11β-HSD1 in peripheral tissues.Transgenic animal models have highlighted the critical role of 11β-HSD1 in the regulation of metabolic phenotype in individual tissues. Mice overexpressing 11β-HSD1, specifically in adipose tissue, develop visceral obesity, insulin resistance, dyslipidemia, and hypertension (9, 10). Similarly, liver-specific 11β-HSD1 overexpression results in insulin resistance and hypertension, but not obesity (11). Importantly, circulating CORT levels were not elevated in either model, suggesting increased intracellular GC availability underpins the observed phenotypes. Indeed, this was confirmed in the adipose-specific 11β-HSD1–overexpressing mice, where twofold higher intraadipose CORT levels were recorded in comparison with WT controls (9). Ultimately, this has led to the development of selective 11β-HSD1 inhibitors as a potential treatment for patients with diabetes, obesity, and hypertension (12, 13).Although it is clear that 11β-HSD1 has a critical role to play in governing GC availability, its potential dynamic role in the setting of GC excess has not been fully explored (14–16). We have previously reported a patient with Cushing disease who was protected from the classic Cushing phenotype, owing to a functional defect in 11β-HSD1 activity, as evidenced by serum and urinary biomarkers (17). Based on this observation, we have hypothesized that tissue intrinsic 11β-HSD1 activity is the major determinant of the manifestations of GC excess and that 11β-HSD1 deletion will ameliorate the associated metabolic abnormalities. To determine the relative tissue-specific contribution to this effect, we have generated tissue-specific 11β-HSD1 deletions in liver and adipose tissue. 相似文献
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Gabriele Simonini Druce Katie Rolando Cimaz Gary J. Macfarlane Gareth T. Jones 《Seminars in arthritis and rheumatism》2014
Objective
To summarize the evidence regarding the effectiveness of switching to a second anti-TNFα treatment in children with autoimmune chronic uveitis (ACU), refractory to the first course of anti-TNFα treatment.Methods
We conducted a systematic literature review between January 2000 and May 2013 to investigate the efficacy of a second anti-TNFα agent in the treatment of ACU in children (≤16 years) refractory to a first course of a single anti-TNFα treatment, topical and/or systemic steroid therapy and at least one DMARD. The primary outcome measure was the improvement of intraocular inflammation, as defined by the SUN working group criteria, at 6 (±2) months of treatment.Results
Among 1086 identified articles, 128 were scrutinized: 10 observational studies, 6 on adalimumab (ADA), 3 on infliximab (INF), and 1 on both, were deemed eligible. Study cohort included 40 children (ADA = 34 and INF = 6), median age 8 years (range 3–16). Nine were males, 28 females (gender not reported in 3), 39/40 were affected by JIA. Seventeen children received etanercept: 11 were switched to ADA, the remaining 6 to INF. All 23 children who previously received INF were switched to ADA. Altogether, 30 children (24 on ADA, 6 on INF) of 40 responded to treatment: 0.75 (95% CI: 0.51–100) was the combined estimate of the proportion of subjects improving.Conclusions
Despite the fact that no RCT is available and the number of cases is small, this review provides evidence that switching to a second anti-TNFα agent results in improvement of ocular activity for the 75% treated children 相似文献78.
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Ponsford MJ Medana IM Prapansilp P Hien TT Lee SJ Dondorp AM Esiri MM Day NP White NJ Turner GD 《The Journal of infectious diseases》2012,205(4):663-671
The pathogenesis of coma in severe Plasmodium falciparum malaria remains poorly understood. Obstruction of the brain microvasculature because of sequestration of parasitized red blood cells (pRBCs) represents one mechanism that could contribute to coma in cerebral malaria. Quantitative postmortem microscopy of brain sections from Vietnamese adults dying of malaria confirmed that sequestration in the cerebral microvasculature was significantly higher in patients with cerebral malaria (CM; n = 21) than in patients with non-CM (n = 23). Sequestration of pRBCs and CM was also significantly associated with increased microvascular congestion by infected and uninfected erythrocytes. Clinicopathological correlation showed that sequestration and congestion were significantly associated with deeper levels of premortem coma and shorter time to death. Microvascular congestion and sequestration were highly correlated as microscopic findings but were independent predictors of a clinical diagnosis of CM. Increased microvascular congestion accompanies coma in CM, associated with parasite sequestration in the cerebral microvasculature. 相似文献
80.
Söderhjelm P Tribello GA Parrinello M 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(14):5170-5175
A molecular dynamics-based protocol is proposed for finding and scoring protein-ligand binding poses. This protocol uses the recently developed reconnaissance metadynamics method, which employs a self-learning algorithm to construct a bias that pushes the system away from the kinetic traps where it would otherwise remain. The exploration of phase space with this algorithm is shown to be roughly six to eight times faster than unbiased molecular dynamics and is only limited by the time taken to diffuse about the surface of the protein. We apply this method to the well-studied trypsin-benzamidine system and show that we are able to refind all the poses obtained from a reference EADock blind docking calculation. These poses can be scored based on the length of time the system remains trapped in the pose. Alternatively, one can perform dimensionality reduction on the output trajectory and obtain a map of phase space that can be used in more expensive free-energy calculations. 相似文献