Human Platelet Lysate for Good Manufacturing Practice-Compliant Cell Production

Numerous cell-based therapeutics are currently being tested in clinical trials. Human platelet lysate (HPL) is a valuable alternative to fetal bovine serum as a cell culture medium supplement for a variety of different cell types. HPL as a raw material permits animal serum-free cell propagation with highly efficient stimulation of cell proliferation, enabling humanized manufacturing of cell therapeutics within a reasonable timeframe. Providers of HPL have to consider dedicated quality issues regarding identity, purity, potency, traceability and safety. Release criteria have to be defined, characterizing the suitability of HPL batches for the support of a specific cell culture. Fresh or expired platelet concentrates from healthy blood donors are the starting material for HPL preparation, according to regulatory requirements. Pooling of individual platelet lysate units into one HPL batch can balance donor variation with regard to essential platelet-derived growth factors and cytokines. The increasingly applied pathogen reduction technologies will further increase HPL safety. In this review article, aspects and regulatory requirements of whole blood donation and details of human platelet lysate manufacturing are presented. International guidelines for raw materials are discussed, and defined quality controls, as well as release criteria for safe and GMP-compliant HPL production, are summarized.     

Radioprotective effects of basic copper carboxylate complexes

The radioprotective activity of eight selected copper (II) carboxylates--Cu (RCOO)2.nL (R = alkyl, aryl, 2-furyl and 2-thienyl; L usually represents water)--was assayed in a model of lethally gamma-irradiated (9 Gy, 0.97 Gy/min) mice. The compounds tested were applied (as solutions in saline) s.c. in three single doses of 20 mumol/kg 48.24 and 6 h before irradiation. The highest radioprotective effects were measured by survival of mice achieved after premedication of animals with copper (II) 2-thenoate monohydrate (77%), copper (II) acetylsalicylate (64%), copper (II) 2-methoxybenzoate monohydrate (62%) and copper (II) acetate monohydrate (54%). On the other hand, survival of vehicle-pretreated mice was only 10%. The observed biological properties of complexes are discussed in relation to their structures.     

The inhibition by naphthoquinones and anthraquinones of 2-amino-3-methylimidazo[4,5-f ]quinoline metabolic activation to a mutagen: a structure-activity relationship study

 Nine naphthoquinones, 19 anthraquinones, and nine structurally related monoketonic compounds such as anthrone, xanthone, etc., inhibited mutagenicity induced by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in Salmonella typhimurium TA 98 in the presence of rat liver S9 with distinct structure-activity relationships. A carbonyl function was a prerequisite for antimutagenicity while, in general, anthraquinones (IC₅₀ values: 2.3–>213 nmol/ml top agar) were more potent antimutagens than structurally related monoketonic compounds (IC₅₀ values: 25.3–94.9 nmol/ml top agar) and naphthoquinones (IC₅₀ values: 3.7–90.7 nmol/ml top agar). The parent compounds and methyl substituted derivatives were already the most potent while introduction of polar substituents such as COOH and SO₃H considerably reduced antimutagenicity. Introduction of OH functions had equivocal effects: with increasing numbers, antimutagenic potencies were concomitantly reduced; however, anthraflavic acid, chrysazin, quinizarin, and especially 5,8-dihydroxy-1,4-naphthoquinone were more potent than the parent compounds. The patterns of inhibition by quinones of 7-ethoxyresorufin-O-dealkylase activities in rat liver microsomes, linked to cytochrome P-450-dependent oxidation of IQ to N-hydroxy-IQ (N-OH-IQ), were in general identical with those obtained in the Salmonella/reversion assay except for chrysophanic acid, emodin, and some naphthoquinones which were very potent in this assay (IC₅₀: 0.20–45.0 μM). On the other hand, mutagenicity of N-OH-IQ in S. typhimurium TA 98NR was not inhibited by nonpolar quinones (except 1,4-naphthoquinone) but rather by polar compounds and especially by hydroxyquinones (IC₅₀ values: 5.3–106.7 nmol/ml top agar or not reached). Inhibition of mutagenic activities of IQ, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole, and 3-amino-1-methyl-5H-pyrido[4,3-b]indole by chrysazin, chrysophanic acid, physicon, and purpurin varied, but no clearcut structure-activity relationships of the mutagens were observed. Received: 29 May 1998     

ω‐Phthalimidoalkyl Aryl Ureas as Potent and Selective Inhibitors of Cholesterol Esterase

Cholesterol esterase (CEase), a serine hydrolase thought to be involved in atherogenesis and thus coronary heart disease, is considered as a target for inhibitor development. We investigated recombinant human and murine CEases with a new fluorometric assay in a structure–activity relationship study of a small library of ω‐phthalimidoalkyl aryl ureas. The urea motif with an attached 3,5‐bis(trifluoromethyl)phenyl group and the aromatic character of the ω‐phthalimide residue were most important for inhibitory activity. In addition, an alkyl chain composed of three or four methylene groups, connecting the urea and phthalimide moieties, was found to be an optimal spacer for inhibitors. The so‐optimized compounds 2 [1‐(3,5‐bis(trifluoromethyl)phenyl)‐3‐(3‐(1,3‐dioxoisoindolin‐2‐yl)propyl)urea] and 21 [1‐(3,5‐bis(trifluoromethyl)phenyl)‐3‐(4‐(1,3‐dioxoisoindolin‐2‐yl)butyl)urea] exhibited dissociation constants (K_i) of 1–19 μm on the two CEases and showed either a competitive ( 2 on the human enzyme and 21 on the murine enzyme) or a noncompetitive mode of inhibition. Two related serine hydrolases—monoacylglycerol lipase and fatty acid amide hydrolase—were inhibited by ω‐phthalimidoalkyl aryl ureas to a lesser extent.     

Service robots in hospitals: new perspectives on niche evolution and technology affordances

Changing demands in society and the limited capabilities of health systems have paved the way for robots to move out of industrial contexts and enter more human-centered environments such as health care. We explore the shared beliefs and concerns of health workers on the introduction of autonomously operating service robots in hospitals or professional care facilities. By means of Q-methodology, a mixed research approach specifically designed for studying subjective thought patterns, we identify five potential end-user niches, each of which perceives different affordances and outcomes from using service robots in their working environment. Our findings allow for better understanding resistance and susceptibility of different users in a hospital and encourage managerial awareness of varying demands, needs, and surrounding conditions that a service robot must contend with. We also discuss general insights into presenting the Q-methodology results and how an affordance-based view could inform the adoption, appropriation, and adaptation of emerging technologies.     

You like it,you learn it: affectivity and learning in competitive social role play gaming

Despite the alleged ability of digital game-based learning (DGBL) to foster positive affect and in turn improve learning, the link between affectivity and learning has not been sufficiently investigated in this field. Regarding learning from team-based games with competitive elements, even less is known about the relationship between competitiveness (as a dispositional trait) and induced positive affect. In this media comparison study with between-subject design, participants (N?=?325; high school and college students) learned about the EU’s policy agenda by means of a debate-based method delivered through one of three educational media: a) through a social role-playing game with competitive elements played on computers, b) through a very similar game played without computers and c) through a non-game workshop. Unlike many previous DGBL studies, this study used participant randomization and strived to address the teacher effect and the length of exposure effect, while also using the same learning materials and a very similar educational method for all three treatments. Both games induced comparatively higher generalized positive affect and flow. Participants also learned more with the games. Positive affect, but not flow, mediated the influence of educational media on learning gains. Participants’ competitiveness was partly related to positive affect and experiencing flow but unrelated to learning gains. These outcomes held both when the game was played using computers, as well as without them. The study indicates that the ability of an educational intervention to instigate positive affect is an important feature that should be considered by educational designers.     

Characterization of a new miniCAST with diffusion flame and premixed flame options: Generation of particles with high EC content in the size range 30 nm to 200 nm

Flame-generated soot from miniCAST burners is increasingly being used in academia and industry as engine exhaust soot surrogate for atmospheric studies and instrument calibration. Previous studies have found that elemental carbon (EC) content of miniCAST soot is proportional to the mean particle size. Here, the characterization of a prototype miniCAST generator (5201 Type BC), which was designed to decouple the soot composition from the particle size and produce soot particles with high EC and BC content in a large size range, is reported. This prototype may operate either in a diffusion-flame or a partially premixed-flame mode, an option that was not available in former models. It was confirmed that soot properties, such as EC content and Ångström absorption exponent (AAE), were linked to the overall flame composition. In particular, combustion under fuel-rich conditions provided particles with size coupled to the EC fraction and AAE, i.e. smaller particles exhibited a lower EC fraction and higher AAE. In contrast, with fuel-lean diffusion flames and especially with premixed flames under near overall stoichiometric conditions small particles (down to 30?nm) with high EC/TC ratios (>60%) and low AAE (≈1.4) could be generated even without any thermal after-treatment. This new source might thus serve in the future as a useful surrogate for engine exhaust emissions and help to improve calibration procedures of common aerosol instruments.

Copyright © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC     

Quantitative assessment of alkali silica reaction potential of quartz-rich aggregates: comparison of chemical test and accelerated mortar bar test improved by SEM-PIA

Bulletin of Engineering Geology and the Environment - The alkali silica reaction (ASR), which originates in highly alkaline conditions in concrete where reactive forms of silica are available,...