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1.
Surface modification and characterization of GO/polymer thin coatings as excellent bio-active platforms for tissue regeneration.
Awaja, F, Speranza, G, Kaltenegger, H, Coraça-Huber, D, Lohberger, B
Materials science & engineering. C, Materials for biological applications. 2018;:130-139
Abstract
Osteo-integration and tissue regeneration are vital for the longevity, durability, and unremitting functionality of medical implants/scaffolds implanted in vivo. It's essential for biomaterials used for in vivo implantation to induce the cellular secretion of growth factors, necessary for the desired tissue generation, since the administration of artificial growth factors, in vivo, is largely prohibited. Plasma functionalized (N2 and O2) and stabilized Graphene Oxide (GO) thin layers in a hybrid with amorphous carbon (aC) induced the expression of vascular endothelial growth factor (VEGF) and osteoprotegerin (OPG) growth factors in fibroblasts (hGF) and, more remarkably, in osteoblasts (hFOB) cells confirming the suitability for tissue regeneration and osteo-integration applications. We also observed a negative trend between hGF fibroblasts, but not hFOB osteoblasts, cellular viability and GO presence in the hybrid films that might indicate the phenomenon of oxidative stress. We traced that back to the presence of higher concentrations of carboxyl and the carbonyl groups on the surface of the GO rich coatings. The above described properties provided by GO coatings might be desirable for bio-selectivity applications and for the reduction of the undesired fibrosis process that is associated with medical implants in vivo environment. Moreover, novel plasma functionalized GO/polymer hybrid thin coating hybrid compositions are promising candidates for tissue engineering and bioengineering applications as excellent antimicrobial and anticancer platforms.
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2.
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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3.
Toxicological investigations of "naked" and polymer-entrapped AOT-based gold nanotriangles.
Liebig, F, Moreno, S, Thünemann, AF, Temme, A, Appelhans, D, Koetz, J
Colloids and surfaces. B, Biointerfaces. 2018;:560-567
Abstract
Negatively charged ultrathin gold nanotriangles (AuNTs) were synthesized in a vesicular dioctyl sodium sulfosuccinate (AOT)/phospholipid-based template phase. These "naked" AuNTs with localized surface plasmon resonances in the NIR region at about 1300 nm and special photothermal properties are of particular interest for imaging and hyperthermia of cancerous tissues. For these kinds of applications the toxicity and the cellular uptake of the AuNTs is of outstanding importance. Therefore, this study focuses on the toxicity of "naked" AOT-stabilized AuNTs compared to polymer-coated AuNTs. Polymeric coating consisted of non-modified hyperbranched poly(ethyleneimine) (PEI), maltose-modified poly(ethyleneimine) (PEI-Mal) and heparin. The toxicological experiments were carried out with two different cell lines (embryonic kidney carcinoma cell line HEK293T and NK-cell leukemia cell line YTS). This study revealed that the heparin-coating of AuNTs improved biocompatibility by a factor of 50 when compared to naked AuNTs. Of note, the highest nontoxic concentration of the AuNTs coated with PEI and PEI-Mal is drastically decreased. Overall, this is mainly triggered by the different surface charges of polymeric coatings. Therefore, AuNTs coated with heparin were selected to carry out uptake studies. Their promising high biocompatibility and cellular uptake may open future studies in the field of biomedical applications.
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4.
Low fermentable oligo-di-mono-saccharides and polyols diet versus general dietary advice in patients with diarrhea-predominant irritable bowel syndrome: A randomized controlled trial.
Zahedi, MJ, Behrouz, V, Azimi, M
Journal of gastroenterology and hepatology. 2018;(6):1192-1199
Abstract
BACKGROUND AND AIM Recent evidence indicates that new approach of the diet with low fermentable oligo-di-mono-saccharides and polyols (FODMAPs) may have an effective role in management of the patients with irritable bowel syndrome (IBS). We compared the results of low FODMAP diet with current dietary treatment, general dietary advices (GDA), on the clinical response in patients with diarrhea subtype of IBS (IBS-D). METHODS In this randomized, controlled, single-blind trial, we included 110 patients with IBS-D in two intervention groups. Participants were randomly assigned to the low FODMAP diet (n = 55) and GDA (n = 55) for 6 weeks after a 10-day screening period. Gastrointestinal symptoms and bowel habit status were evaluated using a symptom severity scoring system and Bristol stool form scale pre-intervention and post-intervention. Patients completed 3-day food diary before and after the intervention. RESULTS Of 110 patients, 101 completed the dietary interventions. At the baseline, the nutrient intake, severity of symptoms, and demographic data were similar between two groups. After 6 weeks, the low FODMAP diet improves significantly overall gastrointestinal symptoms scores, stool frequency, and consistency versus GDA group (P < 0.001, P < 0.001, and P = 0.003, respectively). Compared with the baseline, both intervention groups expressed a significant reduction in overall scores of symptom severity scoring system, abdominal pain, distension, consistency, and frequency, but this reduction is greater in low FODMAP diet group. CONCLUSIONS Both low FODMAP diet and GDA in patients with IBS-D led to adequate improvement of gastrointestinal symptoms for 6 weeks. However, the low FODMAP diet has greater benefits in IBS improvement.
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5.
Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease Patients Taking RAAS Inhibitors.
Weir, MR, Bushinsky, DA, Benton, WW, Woods, SD, Mayo, MR, Arthur, SP, Pitt, B, Bakris, GL
The American journal of medicine. 2018;(5):555-564.e3
Abstract
BACKGROUND Older people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin-angiotensin-aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK. METHODS Chronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo. RESULTS Mean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was -1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A). CONCLUSIONS Patiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi.
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6.
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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7.
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.
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8.
A Pilot Study to Evaluate the Effects of Topically Applied Cosmetic Creams on Epidermal Responses.
Kelchen, MN, Menon, G, Ten Eyck, P, Prettypaul, D, Brogden, NK
Skin pharmacology and physiology. 2018;(5):269-282
Abstract
Application of exogenous products, such as creams, to the skin can result in subclinical changes in selected epidermal functions such as transepidermal water loss (TEWL), hydration, redness, and pH; these changes may lead to or contribute to irritation. Changes in skin surface inflammatory factors may provide further insight into this potential for irritation. The objective of this study was to evaluate the changes in epidermal properties and inflammatory mediators after 4 days of topical application of 2 different polymers formulated in cosmetic creams. Ten healthy volunteers (mean age ± SD: 20.0 ± 2.4 years) completed the study. TEWL, color, and pH were not significantly different after repeated application of these polymers. Hydration was significantly lower at sites treated with polymer A after 5 days. Significant increases in IL-1α, IL-1RA, and IL-1β were observed after cream application at sites treated with polymer A. This is the first study to apply noninvasive measurements to quantify subclinical changes in epidermal properties and inflammatory mediator expression before and after the application of a cosmetic product, which will allow for a more enhanced safety profile to be achieved.
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9.
Subgroup Analysis Comparing Ultrathin, Bioresorbable Polymer Sirolimus-Eluting Stents Versus Thin, Durable Polymer Everolimus-Eluting Stents in Acute Coronary Syndrome Patients.
Roguin, A, Kandzari, DE, Marcusohn, E, Koolen, JJ, Doros, G, Massaro, JM, Garcia-Garcia, HM, Bennett, J, Gharib, EG, Cutlip, DE, et al
Circulation. Cardiovascular interventions. 2018;(10):e007331
Abstract
BACKGROUND Presentation with acute coronary syndromes (ACS) constitutes a high-risk subset of patients with worse outcome after percutaneous coronary intervention. We report clinical outcomes in subjects with ACS from the BIOFLOW V trial (BIOTRONIK - A Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects With up to Three De Novo or Restenotic Coronary Artery Lesions) comparing an ultrathin strut (60 μm) bioresorbable polymer sirolimus-eluting stent (BP-SES) with a thin strut (81 μm) durable polymer everolimus-eluting stent (DP-EES). METHODS AND RESULTS Among 1334 patients randomized to 2:1 treatment with either BP-SES or DP-EES, 677 (50.7%) ACS patients without ST-segment-elevation myocardial infarction (MI; 454 BP-SES and 223 DP-EES) were identified in the retrospective post hoc analysis. The primary end point of 12-month target lesion failure, individual component end points, and stent thrombosis were evaluated. Recurrent MI was defined as a ≥50% increase of creatine kinase-myocardial band or in the absence of creatine kinase-myocardial band, troponin >50% increase over previous level and >3× the upper limit of normal). All events were adjudicated by a blinded independent clinical events committee. Overall, baseline clinical, angiographic, and procedural characteristics of the ACS population were similar between the 2 treatment groups. At 12 months, target lesion failure occurred in 5.6% (24/426) of BP-SES patients versus 11.0% (23/209) in DP-EES patients ( P=0.02); target lesion failure composite components were cardiac death, 0% versus 1.0% ( P=0.11); target vessel-related MI, 3.5% versus 9.7% ( P=0.003); and clinically driven target lesion revascularization, 2.8% versus 3.4% ( P=0.80). Spontaneous target vessel MI was 0.5% (2/425) for BP-SES versus 2.4% (5/206) for DP-EES ( P=0.041). Stent thrombosis rates at 1 year were similar (0.5% versus 1.0%; P=0.601). CONCLUSIONS In the ACS subgroup population of the BIOFLOW V study, treatment with BP-SES compared with DP-EES was associated with a significantly lower rate of 12-month target lesion failure, a difference driven by significantly lower periprocedural MI and spontaneous MI. These findings support treatment with an ultrathin strut BP-SES in ACS patients undergoing percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT02389946.
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10.
Advances in Stimulus-Responsive Polymeric Materials for Systemic Delivery of Nucleic Acids.
Sun, M, Wang, K, Oupický, D
Advanced healthcare materials. 2018;(4)
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Abstract
Polymeric materials that respond to a variety of endogenous and external stimuli are actively developed to overcome the main barriers to successful systemic delivery of therapeutic nucleic acids. Here, an overview of viable stimuli that are proved to improve systemic delivery of nucleic acids is provided. The main focus is placed on nucleic acid delivery systems (NADS) based on polymers that respond to pathological or physiological changes in pH, redox state, enzyme levels, hypoxia, and reactive oxygen species levels. Additional discussion is focused on NADS suitable for applications that use external stimuli, such as light, ultrasound, and local hyperthermia.