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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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[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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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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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.
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Potential of chitosan-based carrier for periodontal drug delivery.
Sah, AK, Dewangan, M, Suresh, PK
Colloids and surfaces. B, Biointerfaces. 2019;:185-198
Abstract
Periodontal diseases are chronic infectious diseases and are a major oral health burden. With the progress in the understanding of etiology, epidemiology and pathogenesis of periodontal diseases coupled with the understanding of the polymicrobial synergy in the dysbiotic oral microbial flora, several new therapeutic targets have been identified. The strategies to curb bacterial growth and production of factors that gradually destroy the tissue surrounding and supporting the teeth have been the cornerstone for inhibiting periodontitis. Systemic administration of antibiotics for the treatment of periodontitis have shown several drawbacks including: inadequate antibiotic concentration at the site of the periodontal pocket, a rapid decline of the plasma antibiotic concentration to sub-therapeutic levels, the development of microbial resistance due to sub-therapeutic drug levels and peak-plasma antibiotic concentrations which may be associated with various side effects. These obvious disadvantages have evoked an interest in the development of localized drug delivery systems that can provide an effective concentration of antibiotic at the periodontal site for the duration of the treatment with minimal side effects. A targeted sustained release device which could be inserted in the periodontal pocket and prolong the therapeutic levels at the site of action at a much lower dose is the need of the hour. Chitosan, a deacetylated derivative of chitin has attracted considerable attention owing to its special properties including antimicrobial efficacy, biodegradability, biocompatibility and non-toxicity. It also has the propensity to act as hydrating agent and display tissue healing and osteoinducting effect. The aim of this review is to shine a spotlight on the chitosan based devices developed for drug delivery application in the effective treatment of various periodontal disorders. The chitosan based carriers like fibers, films, sponge, microparticles, nanoparticles, gels that have been designed for sustained release of drug into the periodontal pocket are highlighted.
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Dietary Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Gastrointestinal Disease.
Vakil, N
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2018;(4):468-475
Abstract
FODMAP is an acronym for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Dietary modification of FODMAPs has been shown to have significant effects on the physiology of the gastrointestinal tract and improves symptoms of abdominal pain, distention, and bloating in patients with irritable bowel syndrome. Structured withdrawal and reintroduction of FODMAPs supervised by a dietitian is the optimal practice for dietary FODMAP modification in irritable bowel syndrome. FODMAPs are present in enteral feeding formulas and may have a role in diarrhea and bloating in tube-fed patients. Emerging areas of research include the effects of dietary modification of FODMAPs on the microbiome, micronutrient absorption, and caloric intake. FODMAP dietary modification is an emerging area in other gastrointestinal disorders and is of relevance to all practicing dietitians.
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Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers.
Ruff, KM, Roberts, S, Chilkoti, A, Pappu, RV
Journal of molecular biology. 2018;(23):4619-4635
Abstract
Proteins and synthetic polymers can undergo phase transitions in response to changes to intensive solution parameters such as temperature, proton chemical potentials (pH), and hydrostatic pressure. For proteins and protein-based polymers, the information required for stimulus-responsive phase transitions is encoded in their amino acid sequence. Here, we review some of the key physical principles that govern the phase transitions of archetypal intrinsically disordered protein polymers (IDPPs). These are disordered proteins with repetitive amino acid sequences. Advances in recombinant technologies have enabled the design and synthesis of protein sequences of a variety of sequence complexities and lengths. We summarize insights that have been gleaned from the design and characterization of IDPPs that undergo thermo-responsive phase transitions and build on these insights to present a general framework for IDPPs with pH and pressure responsive phase behavior. In doing so, we connect the stimulus-responsive phase behavior of IDPPs with repetitive sequences to the coil-to-globule transitions that these sequences undergo at the single-chain level in response to changes in stimuli. The proposed framework and ongoing studies of stimulus-responsive phase behavior of designed IDPPs have direct implications in bioengineering, where designing sequences with bespoke material properties broadens the spectrum of applications, and in biology and medicine for understanding the sequence-specific driving forces for the formation of protein-based membraneless organelles as well as biological matrices that act as scaffolds for cells and mediators of cell-to-cell communication.
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Ion-Responsive Drug Delivery Systems.
Yoshida, T, Shakushiro, K, Sako, K
Current drug targets. 2018;(3):225-238
Abstract
BACKGROUND Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. OBJECTIVE The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. RESULTS Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. CONCLUSION Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world.