The aquaporin-1 (AQP1) water channel is a potentially important drug target, as AQP1 inhibition is predicted to have therapeutic action in edema, tumor growth, glaucoma, and other conditions. Here, ...we measured the AQP1 inhibition efficacy of 12 putative small-molecule AQP1 inhibitors reported in six recent studies, and one AQP1 activator. Osmotic water permeability was measured by stopped-flow light scattering in human and rat erythrocytes that natively express AQP1, in hemoglobin-free membrane vesicles from rat and human erythrocytes, and in plasma membrane vesicles isolated from AQP1-transfected Chinese hamster ovary cell cultures. As a positive control, 0.3 mM HgCl2 inhibited AQP1 water permeability by >95%. We found that none of the tested compounds at 50 µM significantly inhibited or increased AQP1 water permeability in these assays. Identification of AQP1 inhibitors remains an important priority.
The article “Possible Mechanisms of Long-Term Trend of June Rainfall over the Korean Peninsula”, written by Hyeran Lee, Hwan-Jin Song and Byung-Ju Sohn, was originally published electronically on the ...publisher’s internet portal on 08 January 2020 without open access.
Intestinal enteroids are ex vivo primary cultured single-layer epithelial cell spheroids of average diameter ∼150 μm with luminal surface facing inward. Measurement of enteroid swelling in response ...to secretagogues has been applied to genetic testing in cystic fibrosis and evaluation of drug candidates for cystic fibrosis and secretory diarrheas. The current measurement method involves manual addition of drugs and solutions to enteroids embedded in a Matrigel matrix and estimation of volume changes from confocal images of fluorescently stained enteroids. We developed a microfluidics platform for efficient trapping and immobilization of enteroids for quantitative measurement of volume changes. Multiple enteroids are trapped in a “pinball machine-like” array of polydimethylsiloxane posts for measurement of volume changes in unlabeled enteroids by imaging of an extracellular, high-molecular weight fluorescent dye. Measurement accuracy was validated using slowly expanding air bubbles. The method was applied to measure swelling of mouse jejunal enteroids in response to an osmotic challenge and cholera toxin-induced chloride secretion. The microfluidics platform allows for parallel measurement of volume changes on multiple enteroids during continuous superfusion, without an immobilizing matrix, and for quantitative volume determination without chemical labeling or assumptions about enteroid shape changes during swelling.
Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous ...system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-likelike 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The
disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.
Objective: The purpose of this study was to investigate the effects of a nanostructured calcium coating on the surfaces of blasted Ti implants on peri‐implant bone formation in the rabbit tibiae.
...Material and methods: Threaded implants (3.75 mm in diameter, 6 mm in length) were roughened by hydroxyapatite (HA) blasting (control; blasted implants). The implants were then hydrothermally treated in a Ca‐containing solution for 24 h to prepare Ca‐incorporated Ti surfaces (experimental; blasted/Ca implants). Surface characterizations were performed by scanning electron microscopy and stylus profilometry before and after Ca coating. Forty‐two implants (21 control and 21 experimental) were placed in the proximal tibiae of seven New Zealand White rabbits. Each rabbit received six implants. To evaluate the effects of the nanostructured Ca coating on the peri‐implant bone‐healing response, removal torque tests and histomorphometric analyses were performed 6 weeks after surgery.
Results: The Ca coating did not significantly change the surface properties produced by blasting at the micron level. Histologically, active bone apposition was observed in the blasted/Ca implants in the marrow space. Compared with the blasted implants, the blasted/Ca implants showed significantly increased bone‐to‐implant contact over the total implant length (P<0.01) and greater mean removal torque values (P<0.05).
Discussion and conclusion: The nanostructured, Ca‐incorporated surface significantly enhanced the peri‐implant bone‐healing response of HA‐blasted Ti implants. It may be concluded that the use of nanostructured, Ca‐coated surfaces may have synergic effects in enhancing osseointegration of blasted Ti implants due to their micron‐scaled surface properties and biologically active surface chemistry.
The fast Radiative Transfer for Television Infrared Observation Satellite (TIROS) Operational Vertical Sounder (RTTOV) (Version 9.3) model was used for simulating the effect of East Asian dust on top ...of atmosphere radiances. The size distribution of Asian dust was retrieved from nine years of sky radiometer measurements at Dunhunag located in the east of Taklimakan desert of China. The default surface emissivity in RTTOV was replaced by the geographically and monthly varying data from University of Wisconsin (UW)/Cooperative Institute for Meteorological Satellite Studies (CIMSS) infrared surface spectral emissivities. For a given size distribution and surface emissivity, the effects of three refractive indices of Optical Properties of Aerosols and Clouds (OPAC) mineral aerosol, dust‐like aerosol by Volz, and High Resolution Transmission (HITRAN) quartz were examined. Results indicate that the specification of surface emissivity using geographically and monthly varying UW/CIMSS data significantly improved the performance of the simulation of AIRS brightness temperature (TB) difference (BTD) between window channels, in comparison to the results from the use of default emissivity value of 0.98 in the RTTOV model, i.e., increase of the correlation coefficient from 0.1 to 0.83 for BTD between 8.9 μm and 11 μm, and from 0.31 to 0.61 for BTD between 3.8 μm and 11 μm. On the other hand, the use of Asian dust size distributions contributed to a general reduction of radiance biases over dust‐sensitive window bands. A further improvement of the TB simulations has been made by considering the Volz refractive index, suggesting that hyperspectral infrared remote sensing of Asian dust can be improved using the proper optical properties of the dust and surface emissivity.
Key Points
Improvement of hyperspectral IR radiance simulation under Asian dust
Mie calculation based on estimated size distribution for Asian dust
Finding best available IR refractive index for Asian dust simulation
Rhegmatogenous retinal detachment (RRD) frequency was observed to be higher with an increase in the daily temperature range. This showed that a wide daily range of temperature, rather than the ...absolute value of the temperature, is associated with the occurrence of RRD. Purpose. To investigate the association between the frequency of rhegmatogenous retinal detachment (RRD) and the atmospheric temperature. Method. A retrospective review of consecutive eyes that had undergone primary RRD surgery from 1996 to 2016 at Chungbuk National University Hospital was conducted. Temperature data (highest, lowest, and mean daily temperatures and daily temperature range) in Chungbuk Province were obtained from the Korean Meteorological Administration database. We investigated the relationship between the daily temperature range and the frequency of RRD surgery. We also analyzed the association between various temperature data and the frequency of RRD surgery. Result. There were 1,394 RRD surgeries from 1996 to 2016. Among them, 974 eyes were included in this study. The monthly average number of RRD operations showed a bimodal peak (in April and October) throughout the year. With the same tendency as the frequency of RRD, the monthly average of the daily temperature range over 1 year also showed a bimodal peak in April and October. There was a significant positive correlation between the monthly average of the daily temperature range and the number of RRD surgeries (r = 0.297, P<0.001). However, there were no associations between RRD frequency and the mean temperature, highest temperature, and lowest temperature. Conclusion. The higher the daily temperature range, the higher was the RRD frequency observed. We speculated that dynamic changes in temperature during the day may affect degrees in chorioretinal adhesion and liquefaction of the vitreous, which may eventually result in retinal detachment. Therefore, further experimental studies on the correlation between temperature changes and retinal detachment are needed.
Background: The purpose of this study was to investigate the association between responses to intravitreal bevacizumab injection and renal function in diabetic macular edema (DME) patients. Methods: ...A retrospective study of the medical records of 104 treatment-naïve DME patients who received intravitreal bevacizumab injection (IVBI) was conducted. Based on the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2), the participants were classified into three groups. Intergroup comparisons of the best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) changes were performed after three-monthly consecutive IVBIs. In the groups with decreased renal function, the response to further treatment with a different drug was investigated. Results: A total of 104 participants were included in the study: 60 participants in the preserved renal function group (eGFR ≥ 60), 25 participants in the moderate chronic kidney disease (CKD) group (30 ≤ eGFR < 60), and 19 participants in the severe CKD group (eGFR < 30). After three-monthly consecutive IVBIs, BCVA (p < 0.001) and CST (p < 0.001) were significantly improved only in the preserved renal function group. Following further treatment of patients with decreased renal function, the treatment results were significantly better in those who were switched to aflibercept or dexamethasone implant than in those who were maintained on IVBI. Conclusions: From this preliminary study, we observed that renal function might affect the response to IVBI treatment in patients with DME. In the case of a poor response to initial IVBI treatment for DME in patients with moderate to severe CKD, our study supports switching to the aflibercept or dexamethasone implant.
Purpose
To investigate the changes in the near reading speed after panretinal photocoagulation (PRP) in diabetic retinopathy patients.
Methods
This non-randomized, prospective, clinical study ...enrolled diabetic retinopathy patients who underwent PRP from January 2016 to June 2017. The near reading speed was measured before and 1 week, 1 month, and 4 months after PRP by using an iPad application for the assessment of reading speed; near best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) were also analyzed. The reading speed of age-matched healthy individuals was compared with that of diabetic retinopathy patients.
Results
Forty-seven patients were enrolled in this study. The baseline near reading speed of diabetic retinopathy patients was significantly slower than that of age-matched healthy controls. The near reading speed was reduced at 1 week after PRP, but recovered at 1 and 4 months after PRP. Near BCVA showed a similar pattern after PRP. SFCT increased at 1 week after PRP and significantly decreased at both 1 and 4 months after PRP.
Conclusion
The near reading speed of diabetic patients was significantly slower than that of age-matched healthy controls. The speed was temporarily reduced at 1 week after PRP, potentially due to short-term impairment of parasympathetic nerve innervation.
Background: To evaluate long-term visual/anatomic outcome after anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with fovea-involving fibrovascular pigment epithelium ...detachment (PED) presenting with choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA). Methods: Patients with fibrovascular PED or subretinal CNV confirmed by OCTA who were treated by a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. The best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) before and after anti-VEGF injection were analyzed. Furthermore, changes in photoreceptor layer (PRL) thickness and outer retinal bands in the fovea after injection were evaluated. Results: A total of 31 eyes with fibrovascular PED and 24 eyes with subretinal CNV were included. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST were improved, and the PRL thickness was decreased significantly. There were no differences in BCVA, CST, changes in PRL thickness, or the status of outer retinal bands between the groups. However, the difference in the amount of decrease in PRL thickness between the two groups was increased at 2 years, and the slope tended to be steeper in the subretinal CNV group. Conclusions: Exudative age-related macular degeneration (AMD) with fibrovascular PED or subretinal CNV showed good visual/anatomic outcomes after anti-VEGF treatment, regardless of the CNV type. By 2 years, fibrovascular PED did not have an additional protective effect on the outer retina, compared with subretinal CNV over 2 years. Further follow-up study might be needed to conclude that fibrovascular PED has a protective effect on the surrounding photoreceptor area.
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