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| 2. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 5. |
- Gong, Y., et al.
(författare)
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Cytochrome P450 Oxidase 2C Inhibition Adds to-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization
- 2016
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Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 36:9, s. 1919-1927
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Tidskriftsartikel (refereegranskat)abstract
- Objective Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of -3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but -3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of -3 LCPUFA on neovascular eye diseases. Approach and Results The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of -3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and -3 LCPUFA-derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of -3 LCPUFA on retinal neovascularization and CNV by 30% and 20%, respectively. In CYP2C8-overexpressing mice fed a -3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C -3 LCPUFA-derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected -3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. Conclusions Inhibition of CYP2C activity adds to the protective effects of -3 LCPUFA on pathological retinal neovascularization and CNV.
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| 6. |
- Friberg, Andrew S, 1979-
(författare)
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Standardization of Islet Isolation and Transplantation Variables
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Currently, the transplantation of islets of Langerhans is a viable means to maintain control of blood sugar levels and reduce the risk of hypoglycemia in defined populations with brittle type I diabetes mellitus or those requiring pancreatectomy. However, the process of islet isolation is highly variable and not all isolations result in islet numbers or quality suitable for transplantation. This thesis aimed to improve transplantation success through optimization and standardization of the isolation process and to identify pretransplant variables associated with early islet engraftment. A previously disregarded enzyme activity, tryptic-like activity (TLA), has been identified to influence pancreas digestion efficiency and islet isolation success in both the preclinical and clinical situations. For human pancreases, islet isolation success rates improved from 0% in the lowest TLA group to over 50% in the highest TLA groups without affecting islet quality. These findings should help standardize evaluation of enzymes for clinical islet isolation. A closed, automated, pump-made gradient system was compared to the open, manual method for islet separation. No differences were observed in expected gradient volumes, islet yields or total purities between the two methods. The pump-made gradient system successfully removed manual influences on density gradient production while fulfilling regulatory requirements for closed system processing. Islet quantification was evaluated with computer-assisted digital imaging analysis (DIA) and a semi-closed assessment system. By using the DIA system method, which measures islet purity and pellet volume instead of manual counting methods, variation in islet counts and purity reduced by almost half. By using a transplant outcome measurement of C-peptide adjusted by blood glucose and creatinine, we identified four pretransplant factors that affect early transplant outcome. Of the four factors, one was related to the organ transport time, one to function of the islets, and two to the transplanted tissue volume. When these four factors were put into a predictive model, it accounted for about 40% of the transplant outcome. The work contained in this thesis identifies and optimizes a number of critical elements related to islet isolation and transplantation protocols.
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| 7. |
- Gong, Y., et al.
(författare)
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Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis
- 2016
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Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 13, s. 201-211
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Tidskriftsartikel (refereegranskat)abstract
- Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)alpha agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP) 2C with higher affinity than to PPAR alpha. CYP2C metabolizes omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). While omega-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both omega-3 and omega-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C omega-3 LCPUFA (and omega-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPAR alpha-/-mice and augmented omega-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic.-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPAR alpha. Fenofibrate augmented the overall protective effects of omega-3 LCPUFAs on neovascular eye diseases. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://reativecommons.org/licenses/by-nc-nd/4.0/).
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| 8. |
- Amizhtan, S. K., et al.
(författare)
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Experimental Study and ANN Analysis of Rheological Behavior of Mineral Oil-Based SiO2 Nanofluids
- 2022
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Ingår i: IEEE transactions on dielectrics and electrical insulation. - : Institute of Electrical and Electronics Engineers (IEEE). - 1070-9878 .- 1558-4135. ; 29:3, s. 956-964
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Tidskriftsartikel (refereegranskat)abstract
- This work reports an experimental and theoretical analysis of the rheological properties of mineral oil-based SiO2 nanofluid for their potential applications in transformer insulation. The flow electrification mechanism on the nanofluids with different surfactants such as cetyl trimethyl ammonium bromide (CTAB), oleic acid, and Span 80 is studied using a spinning disk technique. The results show a higher streaming current for the nanofluids with CTAB as a surfactant compared to oleic acid and Span 80. The rheological behavior of nanofluids is explored with the double gap concentric cylinder geometry. The variation of shear stress with shear rate follows a power law relationship along with a yield stress observed for all the nanofluids. A transition is seen from storage modulus to dominant loss modulus for the nanofluids during the frequency sweep analysis, whereas no transition is observed in the case of mineral oil. In addition, regression analysis using artificial neural network (ANN) algorithms are performed on the experimentally measured viscosity of the nanofluids in order to estimate theoretical parameters and provide insights into the streaming current formation. The desirable rheological characteristics of nanofluids are identified for achieving enhanced insulation performance in transformers.
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| 9. |
- Amizhtan, S. K., et al.
(författare)
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Impact of Magnetic Field on Corona Discharge Behavior of Mineral Oil Under AC Voltage
- 2022
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Ingår i: IEEE transactions on dielectrics and electrical insulation. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 1070-9878 .- 1558-4135. ; 29:4, s. 1417-1424
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Tidskriftsartikel (refereegranskat)abstract
- This article reports an experimental investigation of the impact of magnetic field on corona discharge activity in mineral oil, using both ultrahigh-frequency (UHF) and fluorescence techniques under ac voltage. The results show that corona inception voltage (CIV) increased under ac voltage with varying harmonic frequencies without considering any phase shift and reduced marginally under magnetic field. In addition, the impact of the magnetic field shifted the dominating frequency of the UHF signal (0.9 GHz) obtained under ac voltage toward lower frequencies (0.3 and 0.6 GHz). Under high magnetic fields, the parameters such as rise time, fall time, and pulsewidth of the fluorescence signal increased in its magnitude compared to its effect without a magnetic field. Also, using both the UHF sensor and the fluorescence sensor, there was no clear difference in the phase-resolved partial discharge (PRPD) pattern caused by corona discharge (with and without magnetic field). Furthermore, the number of discharges is observed to be high under the impact of harmonic ac voltages with third- and seventh-order containing total harmonic distortions (THDs) of 4% and 40%.
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| 10. |
- Amizhtan, S. K., et al.
(författare)
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Impact of Surfactants on the Electrical and Rheological Aspects of Silica Based Synthetic Ester Nanofluids
- 2022
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Ingår i: IEEE Access. - : Institute of Electrical and Electronics Engineers (IEEE). - 2169-3536. ; 10, s. 18192-18200
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Tidskriftsartikel (refereegranskat)abstract
- This study reports experimental investigations of the effects of different surfactants (CTAB, Oleic acid and Span 80) on silica based synthetic ester nanofluids. The positive and negative potential observed for the ionic (CTAB) and non-ionic surfactant (Span 80) from zeta potential analysis indicates an improved stability. The optimization of nanofillers and surfactants is performed considering the corona inception voltage measured using ultra high frequency (UHF) technique and fluorescent fiber. Rheological analysis shows no significant variation of properties with shear rate, implying Newtonian behavior even with the addition of surfactant. In addition, the permittivity of the nanofluid is not much affected by adding surfactant but a marginal variation is noticed in the loss tangent with the effect of temperature. The fluorescence spectroscopy shows no change in the emission wavelength with the addition of silica nanofiller and surfactants. Flow electrification studies indicate an increase in the streaming current with the rotation speed and temperature, with a higher current magnitude observed in the case of nanofluids.
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