Friction reducing ability of a poly-l-lysine and dopamine modified hyaluronan coating for polycaprolactone cartilage resurfacing implants

Frictional properties of cartilage resurfacing implants should be sufficiently low to limit damaging of the opposing cartilage during articulation. The present study determines if native lubricious molecule proteoglycan 4 (PRG4) can adsorb onto a layer-by-layer bioinspired coating composed of poly-l-lysine (PLL) and dopamine modified hyaluronic acid (HADN) and thereby can reduce the friction between implant and articular cartilage. An ELISA was developed to quantify the amount of immobilized human recombinant (rh)PRG4 after exposure to the PLL-HADN coating. The effect on lubrication was evaluated by comparing the coefficient of friction (CoF) of bare polycaprolactone (PCL) disks to that of PLL-HADN coated PCL disks while articulated against cartilage using a ring-on-disk geometry and a lubricant solution consisting of native synovial fluid components including rhPRG4. The PLL-HADN coating effectively immobilized rhPRG4. The surface roughness of PCL disks significantly increased while the water contact angle significantly decreased after application of the coating. The average CoF measured during the first minute of bare PCL against cartilage exceeded twice the CoF of the PLL-HADN coated PCL against cartilage. After 60 min, the CoF reached equilibrium values which were still significantly higher for bare PCL compared to coated PCL. The present study demonstrated that PCL can effectively be coated with PLL-HADN. Additionally, this coating reduces the friction between PCL and cartilage when a PRG4-rich lubricant is used, similar to the lubricating surface of native cartilage. This makes PLL-HADN coating a promising application to improve the clinical success of PCL-based cartilage resurfacing implants.</p

Morphology dependent sintering path of nanocrystalline ThO2

status: publishe

Synthesis and sintering studies on the ThO2 fuel cycle front end

status: publishe

AI18F-3p-C-NETA-TATE: Combining a versatile and highly effective chelator with an established somatostatin analogue

Aim/Introduction: Somatostatin-based radiopharmaceuticals (e.g. [68Ga]Ga-DOTATATE and [177Lu]Lu-DOTATATE) have been used to diagnose, monitor, and treat neuroendocrine tumour patients with great success. [18F]AlF-NOTA-octreotide, a promising 18F-labeled somatostatin analogue and potential alternative for 68GaDOTA-peptides, is under clinical evaluation. Ideally, the same precursor (combination of chelator-linker-vector) can be used for production of both diagnostic and therapeutic radiopharmaceuticals with very similar (e.g. Al18F/213Bi/177Lu) or identical (e.g. complementary Tb-radionuclides) pharmacokinetic properties, allowing accurate, personalised dosimetry estimation and radionuclide therapy of NET patients. In this study we evaluate the versatile and highly effective chelator 3p-C-NETA3 and present first results of radiosynthesis and stability of Al[18F]F-3p-C-NETA-TATE. Materials and Methods: 3p-C-NETA was radiolabelled with diagnostic (68Ga, Al18F) or therapeutic  (177Lu,161Tb,213Bi) radionuclides at different temperatures. The in vitro stability of the corresponding radiocomplexes was determined in PBS and human serum at 37 °C. 3p-C-NETA-TATE was synthesised using standard solid-phase peptide synthesis and purifed using HPLC. Al[18F]F-3p-C-NETA-TATE was synthesised in an automated AllInOne module and analysed using radio-HPLC. Finally, the in vitro stability of Al[18F]F-3p-C-NETA-TATE was evaluated in formulation buffer, PBS and human serum at 37 °C. Results: 3p-C-NETA was efficiently labelled with 177Luand 213Bi (RCY>95%) at room temperature and with 161Tb(>95%) and 68Ga (>90%) at 55 °C. Al18F-labeling required a higher temperature of 95 °C to achieve good yields (>85%).The 177Lu- and 161Tb-3p-C-NETA-complex showed excellent invitro stability in both PBS and human serum over a period of eight days (97% intact). We also observed high in vitro stability up to 2 h for Al[18F]F-3p-C-NETA-TATE (>93% intact in PBS and human serum). In contrast, [68Ga]Ga-3p-C-NETA was stable in PBS (>90% intact), but not in human serum (only 60% intact after 2h). Al[18F]F-3p-C-NETA-TATE was obtained in good RCY (56%) and radiochemical purity (98%). Al[18F]F-3pC-NETA-TATE displayed excellent in vitro stability with >95%intact tracer after 4 hours in all tested conditions. Conclusion:  3p-C-NETA is an excellent chelator that can be used for both targeted radionuclide therapy (177Lu, 213Bi and 161Tb) and diagnostic applications (Al18F) and has the potential to replace DOTA analogues in current clinical use. Al[18F]F-3p-CNETA-TATE will be further evaluated using µPET/MRI imaging in healthy rats and SSTR2 positive tumour mice, in a head-to-head comparison with Al18F-NOTA-octreotide.

Acute Hemodynamic Response and Uremic Toxin Removal in Conventional and Extended Hemodialysis and Hemodiafiltration: A Randomized Crossover Study.

BACKGROUND: Intensive hemodialysis (HD) may have significant benefits. the role of extended hemodiafiltration (HDF) has gained interest. The study was to evaluate the acute effects of extended HD and HDF on response and solute removal. STUDY DESIGN: Randomized crossover trial. PARTICIPANTS: Stable patients with end-stage renal disease undergoing conventional HD. INTERVENTION: 13 patients randomly completed a single 4-hour HD (HD4), 4-hour HDF (HDF4), 8-hour HD (HD8), and 8-hour HDF a 2-week interval between study sessions. Between study sessions, received routine conventional HD treatments. OUTCOMES: Acute hemodynamic and uremic toxin clearance. MEASUREMENTS: Blood pressure and heart rate, wave analysis, cardiac output, and microvascular density by sublingual capillaroscopy, as well as relative blood volume and thermal variables, measured. Clearance and removal of uremic toxins also were studied. treatments showed more stability of peripheral systolic blood pressure during HD4, -21.7+/-15.6mm Hg; during HDF4, -23.3+/-20.8mm Hg; during -6.7+/-15.2mm Hg [P=0.04 vs HD4; P=0.08 vs HDF4]; and during HDF8, - Hg [P=0.004 vs HD4; P=0.008 vs HDF4]). A similar observation was found peripheral diastolic and central blood pressures. Cardiac output stable in extended sessions (change during HD4, -1.4+/-1.5L/min; during -1.6+/-1.0L/min; during HD8, -0.4+/-0.9L/min [P=0.02 vs HDF4]; and -0.5+/-0.8L/min [P=0.06 vs HD4; P=0.03 vs HDF4), in line with the relative blood volume slope in long dialysis. No differences in density were found. Energy transfer rates were comparable (HD4, 13.3+/- HDF4, 16.2+/-5.6W; HD8, 14.2+/-6.0W; and HDF8, 14.5+/-4.3W). Small- phosphate removal were superior during long treatments. beta2- fibroblast growth factor 23 (FGF-23) reduction ratios were highest in LIMITATIONS: Small sample size, only acute effects were studied. Treatment time, and not modality, was the determinant for the response. HDF significantly improved removal of middle molecules, with results in extended HDF

Extraction of Am(III) from simulated HAR solution by soft-donor ligand dissolved in [A336][NO3] ionic liquid / molecular diluent mixtures

Orientadora: Profª Drª Nina Amália Brancia PagnanDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Ensino de Biologia em Rede Nacional. Defesa : Curitiba, 31/10/2020Inclui referências: p. 33-37Área de concentração: Ensino de BiologiaResumo: Os mitos raciais com origem na ciência foram desenvolvidos na Idade Moderna durante a formação dos estados capitalistas e foram usados para justificar a exploração das populações não europeias, principalmente as negras. Do ponto de vista biológico e genético, não há apoio para a existência de raças na espécie humana, entretanto, ainda persiste a ideia de raça como construção social. Tratamentos e decisões díspares são profusas na sociedade, o que resulta em desigualdade e sustenta o racismo. Nesse contexto, o ensino de Biologia e, dentro dela, particularmente o ensino de Genética, representa uma arma poderosa para a conscientização sobre a inexistência de raças na espécie humana e, dessa forma, contribuir para derrocar o racismo. Em busca de uma aprendizagem significativa sobre o tema, foi elaborado um roteiro de aulas que utiliza materiais de baixo custo. O objetivo da elaboração desses materiais é tornar a aprendizagem mais eficiente, reforçar e aumentar a assimilação dos estudantes através da metodologia lúdica. Esse processo mais dinâmico, usado nos anos iniciais na escola acaba se perdendo no ensino médio e, desse modo, ao reintroduzir uma prática pedagógica que foge do tradicionalismo das aulas expositivas, o aprendizado se torna mais dinâmico e atraente. A elaboração do roteiro de aulas e dos materiais auxiliares, compostos por dados octogonais, quadro de Davenport adaptado, quadro de fototipos, etc. são materiais concretos com a função de trazer o lúdico para aula e suprem a carência de material pedagógico adequado para o ensino médio, em particular com respeito ao ensino da genética de características poligênicas. Além disso, a sequência de aulas propostas visa fornecer aos professores um material que, além de trabalhar os mecanismos de herança e a variabilidade, proporciona um momento de discussão sobre falta de legitimidade da ideia de raças humanas, contribuindo para sua derrocada. Palavras chaves: raça humana, mito, educação.Abstract: The origin of the myth of race can be traced down to the Modern Age with the strengthening of capitalism. Non-european populations, especially africans were exploited in the name of the economic development. The myth of race fused with Darwinism as well as the work of many scientists gave legitimacy to racism. From the biological and genetic point of view, there is no support for the existence of races in the human species although there is the idea of race as a social construction. Racial prejudice and intolerance based on the myth of race are still striking in our society. Within this context biology and particularly genetics provide powerful elements to make students aware of the non-existence of human races, working towards eliminating racism from school and society. In this sense we developed lesson plans, activities and low-cost teaching material. The material is intended to high school students looking for a more dynamic teaching and includes octagonal dice, an adapted Davenport board, and a phototype board. Introducing playful activities in the teaching-learning process enables creativity and integration reintroducing a pedagogical practice that deviates from the traditionalism of expository classes, making learning more dynamic and attractive. Key words: human races, racial myth, educatio