Reactivity tests for supplementary cementitious materials: RILEM TC 267-TRM phase 1

A primary aim of RILEM TC 267-TRM: “Tests for Reactivity of Supplementary Cementitious Materials (SCMs)” is to compare and evaluate the performance of conventional and novel SCM reactivity test methods across a wide range of SCMs. To this purpose, a round robin campaign was organized to investigate 10 different tests for reactivity and 11 SCMs covering the main classes of materials in use, such as granulated blast furnace slag, fly ash, natural pozzolan and calcined clays. The methods were evaluated based on the correlation to the 28 days relative compressive strength of standard mortar bars containing 30% of SCM as cement replacement and the interlaboratory reproducibility of the test results. It was found that only a few test methods showed acceptable correlation to the 28 days relative strength over the whole range of SCMs. The methods that showed the best reproducibility and gave good correlations used the R3 model system of the SCM and Ca(OH)2, supplemented with alkali sulfate/carbonate. The use of this simplified model system isolates the reaction of the SCM and the reactivity can be easily quantified from the heat release or bound water content. Later age (90 days) strength results also correlated well with the results of the IS 1727 (Indian standard) reactivity test, an accelerated strength test using an SCM/Ca(OH)2-based model system. The current standardized tests did not show acceptable correlations across all SCMs, although they performed better when latently hydraulic materials (blast furnace slag) were excluded. However, the Frattini test, Chapelle and modified Chapelle test showed poor interlaboratory reproducibility, demonstrating experimental difficulties. The TC 267-TRM will pursue the development of test protocols based on the R3 model systems. Acceleration and improvement of the reproducibility of the IS 1727 test will be attempted as well

Peroxiredoxin-1 regulates lipid peroxidation in corneal endothelial cells

Corneal transparency is maintained by a monolayer of corneal endothelial cells. Defects in corneal endothelial cells (CEnCs) can be rectified surgically through transplantation. Fuchs' endothelial corneal dystrophy (FECD) is the foremost cause of endothelial dysfunction and the leading indication for transplantation. Increased sensitivity of CEnCs to oxidative stress is thought to contribute to the pathogenesis of FECD through increased apoptosis. In part, this is thought to be due to loss of NRF2 expression: a global regulator of oxidative stress. We demonstrate that expression of the redox sensor, peroxiredoxin 1 (PRDX1) is selectively lost from CEnCs in FECD patient samples. We reveal that expression of PRDX1 is necessary to control the response of CEnCs to agents that cause lipid peroxidation. Iron-dependent lipid peroxidation drives non-apoptotic cell death termed ferroptosis. We establish that the inhibitor of ferroptosis, ferrostatin-1 rescues lipid peroxidation and cell death in CEnCs. Furthermore, we provide evidence that the transcription factor NRF2 similarly regulates lipid peroxidation in CEnCs.National Medical Research Council (NMRC)Published versionThis work was supported by the Singapore National Medical Research Council (NMRC), Clinician Scientist Award (NMRC/CSA-INV/0004/2015). The funding body had no role in study design, nor theanalysis and interpretation of data or the decision to publish

Eye bank prepared versus surgeon cut endothelial graft tissue for Descemet membrane endothelial keratoplasty: An observational study

International audienc

New developments in corneal endothelial cell replacement

Corneal transplantation is currently the most effective treatment to restore corneal clarity in patients with endothelial disorders. Endothelial transplantation, either by Descemet membrane endothelial keratoplasty (DMEK) or by Descemet stripping (automated) endothelial keratoplasty (DS(A)EK), is a surgical approach that replaces diseased Descemet membrane and endothelium with tissue from a healthy donor eye. Its application, however, is limited by the availability of healthy donor tissue. To increase the pool of endothelial grafts, research has focused on developing new treatment options as alternatives to conventional corneal transplantation. These treatment options can be considered as either 'surgery-based', that is tissue-efficient modifications of the current techniques (e.g. Descemet stripping only (DSO)/Descemetorhexis without endothelial keratoplasty (DWEK) and Quarter-DMEK), or 'cell-based' approaches, which rely on in vitro expansion of human corneal endothelial cells (hCEC) (i.e. cultured corneal endothelial cell sheet transplantation and cell injection). In this review, we will focus on the most recent developments in the field of the 'cell-based' approaches. Starting with the description of aspects involved in the isolation of hCEC from donor tissue, we then describe the different natural and bioengineered carriers currently used in endothelial cell sheet transplantation, and finally, we discuss the current 'state of the art' in novel therapeutic approaches such as endothelial cell injection.Ophthalmic researc

Characterization of Human Transition Zone Reveals a Putative Progenitor-Enriched Niche of Corneal Endothelium

10.3390/cells8101244Cells81

Effects of Rho-Associated Kinase (Rock) Inhibitors (Alternative to Y-27632) on Primary Human Corneal Endothelial Cells

(1) Rho-associated coiled-coil protein kinase (ROCK) signaling cascade impacts a wide array of cellular events. For cellular therapeutics, scalable expansion of primary human corneal endothelial cells (CECs) is crucial, and the inhibition of ROCK signaling using a well characterized ROCK inhibitor (ROCKi) Y-27632 had been shown to enhance overall endothelial cell yield. (2) In this study, we compared several classes of ROCK inhibitors to both ROCK-I and ROCK-II, using in silico binding simulation. We then evaluated nine ROCK inhibitors for their effects on primary CECs, before narrowing it down to the two most efficacious compounds—AR-13324 (Netarsudil) and its active metabolite, AR-13503—and assessed their impact on cellular proliferation in vitro. Finally, we evaluated the use of AR-13324 on the regenerative capacity of donor cornea with an ex vivo corneal wound closure model. Donor-matched control groups supplemented with Y-27632 were used for comparative analyses. (3) Our in silico simulation revealed that most of the compounds had stronger binding strength than Y-27632. Most of the nine ROCK inhibitors assessed worked within the concentrations of between 100 nM to 30 µM, with comparable adherence to that of Y-27632. Of note, both AR-13324 and AR-13503 showed better cellular adherence when compared to Y-27632. Similarly, the proliferation rates of CECs exposed to AR-13324 were comparable to those of Y-27632. Interestingly, CECs expanded in a medium supplemented with AR-13503 were significantly more proliferative in (i) untreated vs. AR-13503 (1 μM; * p p p p p < 0.05). Lastly, an ex vivo corneal wound healing study showed a comparable wound healing rate for the final healed area in corneas exposed to Y-27632 or AR-13324. (4) In conclusion, we were able to demonstrate that various classes of ROCKi compounds other than Y-27632 were able to exert positive effects on primary CECs, and systematic donor-match controlled comparisons revealed that the FDA-approved ROCK inhibitor, AR-13324, is a potential candidate for cellular therapeutics or as an adjunct drug in regenerative treatment for corneal endothelial diseases in humans

Quantification of the Posterior Cornea Using Swept Source Optical Coherence Tomography

10.1167/tvst.7.5.2TRANSLATIONAL VISION SCIENCE & TECHNOLOGY7

Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer

To test the hypothesis that polymorphic variants of antioxidant genes modify the risk of pancreatic cancer, we examined seven single-nucleotide polymorphisms (SNPs) of genes coding for superoxide dismutase (SOD) 2, glutathione S-transferase alpha 4 (GSTA4), catalase and glutathione peroxidase in 575 patients with pancreatic adenocarcinoma and 648 healthy controls in a case–control study. Information on risk factors was collected by personal interview and dietary information was collected by a self-administered food frequency questionnaire. Genotypes were determined using the Taqman method. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were estimated by unconditional logistic regression. No significant main effect of genotype was observed. A borderline significant interaction between diabetes and SOD2 Ex2+24T>C CT/TT genotype was observed (Pinteraction = 0.051); the AORs (95% CI) were 0.98 (0.73–1.32) for non-diabetics carrying the CT/TT genotype, 1.73 (0.94–3.18) for diabetics carrying the CC genotype and 3.49 (2.22–5.49) for diabetics carrying the CT/TT genotype compared with non-diabetics carrying the CC genotype. Moreover, the SOD2 −1221G>A AA genotype carriers had a significantly increased risk for pancreatic cancer among those with a low dietary vitamin E intake but decreased risk among those with a high vitamin E intake (Pinteraction = 0.002). There was a non-significant interaction between diabetes and GSTA4 Ex5−64G>A genotypes (Pinteraction = 0.078). No significant interaction between genotype with cigarette smoking or vitamin C intake was observed. These data suggest that genetic variations in antioxidant defenses modify the risk of pancreatic cancer in diabetics or individuals with a low dietary vitamin E intake