Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and decreased muscle endurance. Many insights into the molecular mechanisms of muscle wasting in CKD ...have been obtained. A persistent imbalance between protein degradation and synthesis in muscle causes muscle wasting. During muscle wasting, high levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The myostatin binding to its receptor activin A receptor type IIB stimulates the expression of atrogenes such as atrogin-1 and muscle ring factor 1, members of the muscle-specific ubiquitin ligase family. Impaired mitochondrial function also contributes to reducing muscle endurance. The increased protein-bound uremic toxin, parathyroid hormone, glucocorticoid, and angiotensin II levels that are observed in CKD all have a negative effect on muscle mass and endurance. Among the protein-bound uremic toxins, indoxyl sulfate, an indole-containing compound has the potential to induce muscle atrophy by stimulating ROS-mediated myostatin and atrogenes expression. Indoxyl sulfate also impairs mitochondrial function. Some potential therapeutic approaches based on the muscle wasting mechanisms in CKD are currently in the testing stages.
In order to decrease the amount of air in a polystyrene foam pattern, we replaced the gas in the pattern with argon, and then measured the pattern decomposition rate and mold filling rate in the ...evaporative pattern casting of molten cast iron. The gas substitution in the pattern was performed by keeping the pattern in an argon atmosphere after the pattern was placed in a vacuum vessel under reduced pressure. The amount of air in the pattern after gas substitution was found to decrease with increasing holding times at reduced pressure and in an argon atmosphere. The pattern decomposition rate immediately after pouring tended to increase with increasing holding times at reduced pressure and in the argon atmosphere, however the decomposition rate slowed down and the thermal decomposition gas layer thickness increased with increasing time after pouring. In the initial stage of the mold filling, the mold filling rate tended to be faster with increasing argon atmosphere holding time during gas substitution, and slower with longer flow length of the molten metal. The decomposition rate of the pattern was slower when the pattern was coated after gas substitution than when the pattern was coated before gas substitution, suggesting that gas substitution efficiency is higher without coatings.
Human serum albumin acts as a reservoir and transport protein for endogenous (e.g. fatty acids or bilirubin) and exogenous compounds (e.g. drugs or nutrients) in the blood. The binding of a drug to ...albumin is a major determinant of its pharmacokinetic and pharmacodynamic profile.
The present review discusses recent findings regarding the nature of drug binding sites, drug-albumin binding in certain diseased states or in the presence of coadministered drugs, and the potential of utilizing albumin–drug interactions in clinical applications.
Drug–albumin interactions appear to predominantly occur at one or two specific binding sites. The nature of these drug binding sites has been fundamentally investigated as to location, size, charge, hydrophobicity or changes that can occur under conditions such as the content of the endogenous substances in question. Such findings can be useful tools for the analysis of drug–drug interactions or protein binding in diseased states. A change in protein binding is not always a problem in terms of drug therapy, but it can be used to enhance the efficacy of therapeutic agents or to enhance the accumulation of radiopharmaceuticals to targets for diagnostic purposes. Furthermore, several extracorporeal dialysis procedures using albumin-containing dialysates have proven to be an effective tool for removing endogenous toxins or overdosed drugs from patients.
Recent findings related to albumin–drug interactions as described in this review are useful for providing safer and efficient therapies and diagnoses in clinical settings. This article is part of a Special Issue entitled Serum Albumin.
•Drug binds to some specific binding sites on human serum albumin.•Drug–albumin interactions are changed in diseased states.•Drug–drug interactions at the protein binding level are clinically used to enhance the efficacy of drugs.•Drug–albumin interactions are clinically applied to remove overdosed drugs.
Plasma nitriding is used for materials that are challenging to nitride by conventional techniques. Because of the sputtering effect of positive ions during glow discharge, protective oxide films on ...the surfaces of materials including stainless steels, aluminum alloys, and titanium alloys, can be effectively removed by ion and energetic particle bombardment; thus, nitrogen mass transfer from the plasma into the component subsurface can be achieved effectively. Plasma nitriding therefore has potential applicability to treat high-entropy alloys (HEAs) containing large amounts of strong oxide-forming elements such as chromium. In this study, the effects of plasma nitriding were investigated on the microstructural, mechanical, and corrosion properties of a CoCrFeMnNi HEA with an fcc structure that is soft and ductile. The HEA was produced by melting pure metals and casting. Direct-current plasma nitriding was then performed in a gas mixture of 25% N2 and 75% H2 for 54 ks at 673–823 K under 200 Pa with an auxiliary cathodic screen. After nitriding, the nitrided samples were examined using scanning electron microscopy, X-ray diffraction (XRD), Vickers microhardness testing, electron probe microanalysis, and glow discharge optical emission spectroscopy (GD-OES). After nitriding, GD-OES revealed that the thickness of the nitriding layer tended to increase with increasing nitriding temperature. XRD analysis revealed that an fcc supersaturated solid solution phase was formed on surfaces nitrided below 723 K, whereas a CrN phase was formed on those nitrided above 723 K. The Vickers microhardness of the nitrided sample surfaces reached approximately 1300 HV. Ball-on-disk wear tests revealed that the wear loss of nitrided samples was considerably lower than that for untreated samples. Finally, the pitting corrosion resistance of samples nitrided at 673 K was higher than that of untreated samples.
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•CoCrFeMnNi high-entropy alloys with a soft fcc structure were plasma nitrided.•Fcc supersaturated solid solution phase was formed on alloys nitrided below 723 K.•CrN phase was formed on alloys nitrided above 723 K.•Wear resistance was improved for all nitrided samples.•Corrosion resistance was improved by nitriding at 673 K but not higher temperatures.
Vaccination against COVID-19 has raised concerns about myocarditis in young men, as out-of-hospital cardiac arrest (OHCA) or sudden death after vaccination has been reported sporadically. Common ...features of these cases are occurrence in young men, within a few weeks after vaccination, in patients with no structural heart diseases. Cases of unexplained nocturnal death showed fibrotic or hypertrophied myocardium, and one case of OHCA presented ventricular fibrillation (VF) triggered by a prominent J wave on an automated external defibrillator and histopathologic findings compatible with myocarditis. Both myocarditis and J waves are prevalent in young men, and these cases imply that myocarditis augments J waves, which trigger VFs, and primary electrical disorders are a leading cause of death. To prevent such issues, artificial intelligence (AI)-assisted interpretation of historical electrocardiogram findings may help predict future J wave formation leading to VF, as digital electrocardiogram (ECG) findings are well suited for AI interpretation.
Using polyethylene glycol (PEG) to functionalize liposomes improves their stealth properties and stability in blood. However, PEG is known to induce the accelerated blood clearance (ABC) phenomenon, ...which occurs for multiple doses owing to anti-PEG IgM being produced after the initial injection. In this study, as an alternative to PEG, polysarcosine (PSar) was selected owing to its low antigenicity and its highly dense chains with controllable lengths, similar to PEG. Furthermore, we directly evaluate the potential of PSar for avoiding the ABC phenomenon by comparing PSar with PEG on the same liposome platform, which has similar physicochemical properties such as hydrophobic region, membrane fluidity, and size. PEG- and PSar-liposomes were prepared and characterized for comparison. PSar-liposomes showed similar physicochemical properties to PEG-liposomes in terms of size control, zeta potential, membrane polarity, and fluidity; however, ELISA results showed noticeably lower levels and faster production speeds of both IgM and IgG for PSar-liposomes than for PEG-liposomes. In addition, a pharmacokinetics experiment with multiple injections showed that PSar-PE coating of liposomes may help to circumvent the ABC phenomenon.
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•Chitosan and its derivatives is useful for oxidative stress related diseases.•Chitosan and its derivatives resulted in reduction of hypocholesteremia and uremia.•The low-dose SDACNFs decreased the ...levels of uremic toxins as pro-oxidants.•The low-dose SDACNFs might result in reduction of cardiovascular disease.•The change of oxidative stress was correlated with serum indoxyl sulfate levels.
This review focuses on the in vitro and in vivo antioxidant activities of various chitosan preparations, including those with different molecular weights and degrees of acetylation and the nanofibers produced from them. In in vitro studies, low molecular weight (LMW) chitosan with high degrees of deacetylation has more potent antioxidant properties than those of high molecular weight (HMW) chitosan. On the other hand, HMW chitosan has higher adsorption properties than those of LMW chitosan. On the basis of the in vitro results obtained, the ingestion of chitosan and nanofiber derived from it, with moderate MW and degrees of acetylation results in a significant reduction in oxidative stress in several chronic oxidative stress related diseases such as the metabolic syndrome and renal failure. In the future, chitosan and related nanofibers with presumed antioxidant properties may be used as a new source of antioxidant, as a possible food supplement, as an ingredient or in the pharmaceutical industry.
We recently reported that aripiprazole (ARP), an antipsychotic drug, binds strongly to human serum albumin (HSA), the major drug binding protein in serum. It is known that uremic toxins that ...accumulate during renal disease affect the interaction between HSA and drug binding. In this study, the issue of how uremic toxins (indoxyl sulfate, indole acetic acid and p-cresyl sulfate) affect the binding of ARP to HSA was investigated. Equilibrium dialysis experiments revealed that all uremic toxins inhibited the binding of ARP to HSA although the inhibitory effects differed, depending on the specific uremic toxin. The potency of inhibition can be partially explained by the affinities of uremic toxins to HSA. Fluorescence displacement experiments suggested that ARP as well as all uremic toxins bind to site II of HSA. The inhibitory effects of the toxins on the binding of ARP for the drugs binding to the diazepam subsite are significantly larger, comparing with those for binding to arylpropionic acids subsite. Interestingly, induced circular dichroism (CD) spectra indicated that the spatial orientation of p-cresyl sulfate in the binding pocket is different from that for indoxyl sulfate and indole acetic acid. The limited findings obtained herein are important data in considering the effects of uremic toxins on the pharmacokinetics of ARP and the drugs that bind to site II on HSA, particularly drugs binding to diazepam binding site in site II.
This study utilized the World Health Organization Disability Assessment Schedule version 2 (WHODAS 2.0) to identify vulnerable students and explore the impact of mental and developmental disorders on ...disability.
A total of 156 undergraduates who visited support service offices at large-scale universities in Japan between April 2018 and March 2020 were included.
The 36-item WHODAS 2.0 was administered, and data were gathered regarding mental and developmental disabilities. Mann-Whitney and Kruskal-Wallis tests were conducted.
Parents/guardians typically initiated consultation with student support services. Students whose parents had initiated consultation did not have higher scores in any WHODAS domain except "Life Activities." In every WHODAS domain except "Cognition," the "Mental Disorder" group scored significantly higher than the "No Disorder" group. The addition of "Developmental Disorders" significantly increased WHODAS scores, except in "Mobility."
The WHODAS is a useful tool for identifying vulnerable students.
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