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1.
Advances in management of chronic metabolic acidosis in chronic kidney disease.
Chen, W, Abramowitz, MK
Current opinion in nephrology and hypertension. 2019;(5):409-416
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Abstract
PURPOSE OF REVIEW Chronic metabolic acidosis is a common complication of chronic kidney disease (CKD) and is associated with adverse consequences, such as CKD progression and muscle wasting. We review the findings from recent clinical trials that have examined the effects of sodium bicarbonate therapy and veverimer in patients with CKD and chronic metabolic acidosis. RECENT FINDINGS There are four recent clinical trials on chronic metabolic acidosis of CKD. In a pilot, cross-over study, 6 weeks of sodium bicarbonate therapy improved vascular endothelial function, measured by brachial artery flow-mediated dilation. In a single-center, randomized, open-label study, 6 months of sodium bicarbonate therapy increased muscle mass and lean body mass, and preserved kidney function. The other two clinical trials (phase 1/2 and phase 3 studies) examined the effects of veverimer, which is a hydrochloric acid binder. The phase 3 study showed that 12-weeks of veverimer increased serum bicarbonate levels and might improve physical function. The effects of veverimer on CKD progression, physical function and cardiovascular endpoints as well as its long-term safety are yet to be determined. SUMMARY Recent studies suggest that sodium bicarbonate therapy may improve vascular endothelial function and muscle mass, and preserve renal function. Veverimer increases serum bicarbonate level and could be a potential new therapeutic option for treating chronic metabolic acidosis.
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Atomistic modeling of flexoelectricity in amorphous polymers.
Hu, T, Chen, L, Mao, W
Journal of molecular graphics & modelling. 2019;:147-153
Abstract
In this paper, the amorphous PVDF (Polyvinylidene Fluoride) and PE (Polyethylene) models are established. The relationship between configuration density and temperature is calculated by molecular dynamics simulation. The rationality of model is determined by comparing with the experimentally determined glass transition temperature Tg. Secondly, the strain gradient is applied to the main chain carbon atoms of the amorphous PVDF and PE equilibrium configuration. Electric polarization occurs when the microstructure of the configuration changes. The transverse flexoelectric coefficients μ12 of amorphous PVDF and PE configurations are 1.24×10-9 C/m and -2.63×10-9 C/m, respectively, obtained by fitting the relationship between polarization and strain gradient. Finally, through the micromechanical analysis, the CF2 and CH2 dipoles rotate around the main chain along the inner side of the curved surface under the strain gradient, accompanied by some small structural adjustments. This leads to the electric polarization of the amorphous PVDF and PE configuration. Due to the difference in charge number and electronegativity between the amorphous PVDF and PE groups, the calculated transverse flexoelectric coefficients of the amorphous PVDF and PE are opposite, and the absolute value of the transverse flexoelectric coefficient of PE is greater than that of PVDF.
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[Hyperkalemia in heart failure: new solutions for an old problem].
Romani, S, Porcari, A, Fabris, E, Sinagra, G
Giornale italiano di cardiologia (2006). 2019;(10):543-551
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Abstract
Potassium is the main intracellular ion and its homeostasis is finely regulated by the renal and gastrointestinal tract. Renal failure and hyperkalemia are conditions commonly found in patients with heart failure, the result of a complex interaction between heart and kidney (e.g. cardio-renal syndrome) and the side effects of drugs commonly used for treating heart disease (e.g. renin-angiotensin-aldosterone system inhibitors). Although hyperkalemia increases the risk of heart conduction disorders and life-threatening arrhythmias, its prognostic significance in heart failure is uncertain. Hyperkalemia and progression of renal damage are the main limitations to the introduction and titration of heart failure therapies. New drugs for the prevention and chronic treatment of hyperkalemia allow the introduction and modulation of anti-neurohormonal therapies in patients with heart failure otherwise excluded from these treatments due to excessively high serum potassium levels.This review illustrates the pathophysiological, epidemiological and prognostic aspects of hyperkalemia and analyses the possible treatments for this condition in heart failure patients.
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Gene Delivery Using Lipoplexes and Polyplexes: Principles, Limitations and Solutions.
Hayat, SMG, Farahani, N, Safdarian, E, Roointan, A, Sahebkar, A
Critical reviews in eukaryotic gene expression. 2019;(1):29-36
Abstract
Gene therapy has attracted considerable attention for the treatment of genetic and acquired diseases. Successful gene therapy occurs when the therapeutic genes penetrate targeted cells and become available to the intracellular active site. Currently, a promising approach in gene delivery is the use of nonviral gene delivery vectors that lack immunogenicity but have low toxicity and potential tissue specificity. The widely used, existing nonviral gene vectors are cationic lipids and polymers that can pass across extracellular and intracellular barriers. However, the toxicity of these vectors is a barrier to their use. Currently, the disadvantages of nonviral vectors have been minimized by several modifications. The main purpose of this review is to describe the pros and cons of gene delivery using cationic lipids and polymers.
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Strategies in the design of endosomolytic agents for facilitating endosomal escape in nanoparticles.
Ahmad, A, Khan, JM, Haque, S
Biochimie. 2019;:61-75
Abstract
Nanoparticles (NPs) are one of the leading and promising technologies for gene and drug delivery. However, despite continuous advancements in the delivery of NPs, endosomal escape remains a major issue and a matter of grave concern for developing an efficient and targeted delivery system for therapeutic applications. Most of NPs generally follow endocytic pathway for internalization into the cells. Following the internalization process, NPs must escape into the cell cytoplasm for evading degradation by hydrolytic enzymes present in the lysosomes. Various types of lipids have been used in the past viz. fusogenic lipid dioleoylphosphatidylethanolamine (DOPE), pH-sensitive lipids, cationic lipid and multiple charges containing lipid to escape from endosomes. Recently, several novel polymers, pH-sensitive peptides, proteins and many others endosomolytic agents have been identified and developed for incorporating into gene and drug delivery system to facilitate endosomal escape. In this review, endosomal escape mechanisms of different types of NPs have been discussed in detail and compared with endosomal escape mechanisms of viruses and other synthetic gene delivery systems to escape from endosomes. Also, the designing of endosomolytic agents to facilitate endosomal escape based on different approaches and strategies is explored. Moreover, this review article highlights the recent advancements in the development of NPs equipped with endosomolytic agents including its future directions and applications in the field of nanomedicine.
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Everolimus-Eluting Versus Biolimus-Eluting Stents With Biodegradable Polymers in Unselected Patients Undergoing Percutaneous Coronary Intervention: A Randomized Noninferiority Trial With 1-Year Follow-Up (SORT OUT VIII Trial).
Maeng, M, Christiansen, EH, Raungaard, B, Kahlert, J, Terkelsen, CJ, Kristensen, SD, Carstensen, S, Aarøe, J, Jensen, SE, Villadsen, AB, et al
JACC. Cardiovascular interventions. 2019;(7):624-633
Abstract
OBJECTIVES The aim of this study was to compare the thin-strut biodegradable-polymer everolimus-eluting platinum-chromium stent (EES) with the biodegradable-polymer biolimus-eluting stainless-steel stent (BES). BACKGROUND Currently available drug-eluting coronary stents have been refined to reduce the risk for coronary events following implantation. METHODS This randomized, multicenter, all-comers, noninferiority trial was undertaken at 3 sites in western Denmark. Patients with clinical indications for percutaneous coronary intervention were eligible for inclusion. Patients were randomly assigned (1:1) to either EES or BES. The primary endpoint, target lesion failure, was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a nontarget lesion) and efficacy (target lesion revascularization) at 12 months, analyzed using intention-to-treat principles. The trial was powered to assess target lesion failure noninferiority of the EES compared with the BES with a predetermined noninferiority margin of 3%. RESULTS A total of 1,385 patients were assigned to treatment with EES and 1,369 patients to treatment with BES. The analysis showed that 55 patients (4.0%) assigned to the EES and 60 (4.4%) assigned to the BES met the primary endpoint (absolute risk difference 0.4%; upper limit of 1-sided 95% confidence interval: 1.7%; p < 0.001). CONCLUSIONS At 1-year follow-up, the EES was found to be noninferior to the BES with respect to target lesion failure. (Everolimus-eluting SYNERGY Stent Versus Biolimus-Eluting Biomatrix NeoFlex Stent-SORT-OUT VIII; NCT02093845).
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Thin, Very Thin, or Ultrathin Strut Biodegradable or Durable Polymer-Coated Drug-Eluting Stents: 3-Year Outcomes of BIO-RESORT.
Buiten, RA, Ploumen, EH, Zocca, P, Doggen, CJM, Danse, PW, Schotborgh, CE, Scholte, M, van Houwelingen, KG, Stoel, MG, Hartmann, M, et al
JACC. Cardiovascular interventions. 2019;(17):1650-1660
Abstract
OBJECTIVES The aim of this study was to assess the 3-year safety and efficacy of treating all-comer patients with 3 contemporary drug-eluting stents (DES). BACKGROUND The BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) (TWENTE III) randomized trial (NCT01674803) found similar 1-year safety and efficacy for the 2 biodegradable-polymer DES (i.e., ultrathin-strut cobalt-chromium Orsiro sirolimus-eluting stent [SES] and very-thin-strut platinum-chromium Synergy everolimus-eluting stent) compared with the durable-polymer thin-strut cobalt-chromium Resolute Integrity zotarolimus-eluting stent (ZES). Two-year follow-up suggested that the SES might reduce repeat revascularizations beyond 1 year compared with the ZES. METHODS A total of 3,514 all-comer patients were treated at 4 centers for coronary intervention. The main clinical endpoint, target vessel failure, was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (target vessel revascularization). Secondary endpoints included the individual components of target vessel failure and stent thrombosis. RESULTS Three-year follow-up data were available for 3,393 of 3,514 patients (96.6%). Target vessel failure occurred in 8.5% with SES and 10.0% with ZES (plog rank = 0.22) and in 8.8% with everolimus-eluting stents (vs. ZES, plog rank = 0.32). Rates of cardiac death, target vessel myocardial infarction, and target vessel revascularization were similar between stent groups. Landmark analyses found no statistically significant between-stent difference in repeat revascularization between 1 and 3 years. Definite or probable stent thrombosis rates were low (SES, 1.1%; everolimus-eluting stent, 1.1%; ZES, 0.9%) and similar with all 3 DES. CONCLUSIONS Despite substantial differences in stent backbone and polymer coating, all 3 DES showed favorable 3-year safety and efficacy in all comers, without significant between-stent differences. Further follow-up is required to definitely answer the question of whether one stent might improve clinical outcomes at a later stage.
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Lipid-polymer hybrid nanoparticles: Synthesis strategies and biomedical applications.
Dave, V, Tak, K, Sohgaura, A, Gupta, A, Sadhu, V, Reddy, KR
Journal of microbiological methods. 2019;:130-142
Abstract
This review article is an updated overview on lipid-polymer hybrid nanoparticles (LPHNs) including the various types of LPHNs polymers used in their preparation, various methods of preparation, their physiochemical, in-vitro and in-vivo evaluation parameters and their application in various delivery systems. LPHNs show a combined advantage of biodegradable polymeric nanoparticles and liposomes. LPHNs mainly consist of a biodegradable polymeric material core containing drugs or any substances which are to be encapsulated then this core is further enclosed by a phospholipid layer i.e. lipid PEG layer. LPHNs show good physical strength and biocompatibility. The hybrid structural design can offer various benefits such as controlled particle size, high drug loading, surface functionality with various ligands (antibody fragments, peptides, monoclonal antibodies, aptamers, and folate molecules), and encapsulation of combinational therapeutic agents, showing prolonged release of drug and drug circulates in the blood for longer duration. Significantly, the LPHNs have recently been confirmed as a better drug delivery route and good cellular delivery efficacy of various drugs as compared to polymeric nanoparticles and liposomes.
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Co-enhance bioactive of polymer scaffold with mesoporous silica and nano-hydroxyapatite.
Shuai, C, Xu, Y, Feng, P, Xu, L, Peng, S, Deng, Y
Journal of biomaterials science. Polymer edition. 2019;(12):1097-1113
Abstract
Mesoporous silica Santa Barbara Amorphous-15 (SBA15) and nano-hydroxyapatite (nHA) were introduced in poly-l-lactic acid (PLLA) scaffold fabricated by selective laser sintering to co-enhance the bioactivity. On the one hand, the active elements silicon and calcium released respectively by the degradation of SBA15 and nHA were favorable for stimulating cell response. On the other hand, the hydrated silica gel layer derived from SBA15 could adsorb calcium ions released from nHA, thereby co-promoting apatite nucleation and growth. The experimental results showed that the formation of bone-like apatite on the scaffold was accelerated under simulated body fluid, indicating a good biomineralization capacity. Moreover, the scaffold demonstrated a good cell response in promoting the attachment of cell and the expression of alkaline phosphatase activity. Besides, SBA15 and nHA not only improved the hydrophilicity of the scaffold (the water contact angle changed from 107.4° to 57.8°), but also retarded the pH reduction by neutralizing the acidic hydrolysate of PLLA. These results indicated that the PLLA-SBA15-nHA scaffold may be potential candidates for bone repair.
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Laboratory and clinical evaluation of polymer materials reinforced by fibers used in dentistry.
Brożek, R, Koczorowski, R, Dorocka-Bobkowska, B
European review for medical and pharmacological sciences. 2019;(5):1855-1863
Abstract
OBJECTIVE Fiber-reinforced composites (FRC) because of high strength and a low mass can be widely applied in many fields of dentistry. MATERIALS AND METHODS The types of fibers commonly used in dentistry with the description of physicochemical properties of the reinforcing phase and polymer resin, are specified. The influence of the method of fiber positioning in the sample, their diameter, length and shape of fibers visible in cross-section on the strength of the FRC material, are underlined. The work also paid attention to the volume of the material that occurs as a result of the absorption of water from the oral environment and changes in bonding between matrix and fiber. RESULTS The clinical procedures and a description of failures that may possibly happen in the oral cavity presented in the work, confirm that they allow fabrication of minimally invasive, lightweight, durable and biocompatible materials. At the moment, the only material group that can be used by direct technique to reach high load-bearing capacity restorations is FRC. CONCLUSIONS Long-term treatment effectiveness makes FRCs an alternative to prosthetic restorations whose retention is obtained only as a result of mechanically interlocking to the abutment tooth. The use of FRCs in clinical dentistry is part of value-based medicine.