Der Einfluss von Levetiracetam und Valproinsäure auf Thrombozytenfunktionen beim Menschen:Eine placebokontrollierte Studie

Es wurde die Wirkung von Levetiracetam auf Zellzahlen, Thrombin-Bildung, Fibrinogen-FITC-Bindung und P-Selektin Expression (CD62P) bei 12 Probanden untersucht. Der Versucht wurde unter Levetiracetam 1000 mg, Valproat 500 mg und Placebo durchgeführt. Vor und nach den Prüfsubstanzen gab es keinen Unterschied in der Zellzahl. Die Werte vor und nach Levetiracetameinnahme bei den Thrombozytenfunktionen zeigen keine signifikanten Unterschiede. Nach Valproateinnahme kommt es zu einer signifikanten Steigerung der P-Selektin Expression (p < 0,017) und zu einem signifikanten Abfall (p < 0,012) bei Fibrinogen-FITC-Bindung. Kein Einfluss war für die Thrombin-Bildung gesehen worden. Die Wirkung von Valproat auf die Koagulation und Thrombozyten war bereits durch klinische Beobachtungen bekannt. Mit dieser Studie können die pathophysiologischen Grundlagen genauer erklärt werden. Dagegen konnte in unserer Studie gezeigt werden, dass Levetiracetam keine Wirkung auf die Blutzellzahl und Thrombozytenfunktion gehabt hat. Die Ergebnisse haben Auswirkungen auf die Wahl des Antiepileptikums bei Patienten mit Gerinnungsstörungen

Synthesis, Structural Features and Physical Properties of a Family of Triply Bridged Dinuclear 3d-4f Complexes

New dinuclear MII-LnIII complexes of general formulas [Cu(µ-L)(µ-OAc)Ln(NO3 )2 ]·CH3CN· H2O (LnIII = Gd (1), Tb (2), Dy (3) and Er (4)), [Ni(CH3CN)(µ-L)(µ-OAc)Ln(NO3 )2 ]·CH3CN (LnIII = Nd (5), Gd (6), Tb (7), Dy (8), Er (9) and Y (10)) and [Co(CH3CN)(µ-L)(µ-OAc)Ln(NO3 )2 ]·CH3CN (LnIII = Gd (11), Tb (12), Dy (13), Er (14) and Y (15)) were prepared from the compartmental ligand N,N0 -dimethyl-N,N0 -bis(2-hydroxy-3-formyl-5-bromo-benzyl)ethylenediamine (H2L). In all these complexes, the transition metal ions occupy the internal N2O2 coordination site of the ligand, whereas the LnIII ions lie in the O4 external site. Both metallic ions are connected by an acetate bridge, giving rise to triple mixed diphenoxido/acetate bridged MIILnIII compounds. Direct current (dc) magnetic measurements allow the study of the magnetic exchange interactions between the 3d and 4f metal ions, which is supported by density functional theory (DFT) theoretical calculations for the GdIII - based counterparts. Due to the weak ferromagnetic exchange coupling constants obtained both experimentally and theoretically, the magneto-thermal properties of the less anisotropic systems (compounds 1 and 6) are also studied. Alternating current (ac)magnetic measurements reveal the occurrence of slight frequency dependency of the out-of-phase signal for complexes 8, 9 and 13, while complex 15 displays well-defined maximums below ~6 K.Junta de Andalucía (FQM-195 and the projects of excellence P11-FQM-7756 and A-FQM-172-UGR18)MINECO of Spain (Projects CTQ2014-56312-P and PGC2018-102052-B-C21)University of GranadaUniversity of The Basque Country UPV/EHU (Project GIU14/01

Designing for Shape Memory in Additive Manufacturing of Cu–Al–Ni Shape Memory Alloy Processed by Laser Powder Bed Fusion

Shape memory alloys (SMAs) are functional materials that are being applied in practically all industries, from aerospace to biomedical sectors, and at present the scientific and technologic communities are looking to gain the advantages offered by the new processing technologies of additive manufacturing (AM). However, the use of AM to produce functional materials, like SMAs, constitutes a real challenge due to the particularly well controlled microstructure required to exhibit the functional property of shape memory. In the present work, the design of the complete AM processing route, from powder atomization to laser powder bed fusion for AM and hot isostatic pressing (HIP), is approached for Cu–Al–Ni SMAs. The microstructure of the different processing states is characterized in relationship with the processing parameters. The thermal martensitic transformation, responsible for the functional properties, is analyzed in a comparative way for each one of the different processed samples. The present results demonstrate that a final post–processing thermal treatment to control the microstructure is crucial to obtain the expected functional properties. Finally, it is demonstrated that using the designed processing route of laser powder bed fusion followed by a post–processing HIP and a final specific thermal treatment, a satisfactory shape memory behavior can be obtained in Cu–Al–Ni SMAs, paving the road for further applications.This research was supported by the Industry Department of the Basque Government through the ELKARTEK–CEMAP (KK–2020/00047) project, as well as from the GIU–17/071 from the University of the Basque Country UPV/EHU. Financial support was also received from the Spanish Ministry of Economy and Competitiveness, MINECO, through the project MAT2017-84069P. This work made use of the facilities from the Electronic Microscopy and Material Microanalysis Service of the SGIKER from the UPV/EHU. M.P.-C. acknowledges the pre–doctoral grant (PRE_2019_2_0268) from the Education Department of the Basque Country. J.F.G.-C. thanks the post–doctoral grant (ESPDOC18/37) from the UPV/EHU

Designing for shape memory in additive manufacturing of Cu-Al-Ni shape memory alloy processed by laser powder bed fusion

Shape memory alloys (SMAs) are functional materials that are being applied in practically all industries, from aerospace to biomedical sectors, and at present the scientific and technologic communities are looking to gain the advantages offered by the new processing technologies of additive manufacturing (AM). However, the use of AM to produce functional materials, like SMAs, constitutes a real challenge due to the particularly well controlled microstructure required to exhibit the functional property of shape memory. In the present work, the design of the complete AM processing route, from powder atomization to laser powder bed fusion for AM and hot isostatic pressing (HIP), is approached for Cu-Al-Ni SMAs. The microstructure of the different processing states is characterized in relationship with the processing parameters. The thermal martensitic transformation, responsible for the functional properties, is analyzed in a comparative way for each one of the different processed samples. The present results demonstrate that a final post-processing thermal treatment to control the microstructure is crucial to obtain the expected functional properties. Finally, it is demonstrated that using the designed processing route of laser powder bed fusion followed by a post-processing HIP and a final specific thermal treatment, a satisfactory shape memory behavior can be obtained in Cu-Al-Ni SMAs, paving the road for further applications

Irida-β-ketoimines derived from Hydrazines to Afford Metallapyrazoles or N-N Bond Cleavage: A Missing Metallacycle Disclosed by a Theoretical and Experimental Study

Unprecedented metallapyrazoles [IrH2{Ph2P(o-C6H4)CNNHC(o-C6H4)PPh2}] (3) and [IrHCl{Ph2P(o-C6H4)CNNHC(o-C6H4)PPh2}] (4) were obtained by the reaction of the irida-β-ketoimine [IrHCl{(PPh2(o-C6H4CO))(PPh2(o-C6H4CNNH2))H}] (2) in MeOH heated at reflux in the presence and absence of KOH, respectively. In solution, iridapyrazole 3 undergoes a dynamic process due to prototropic tautomerism with an experimental barrier for the exchange of ΔGcoal⧧ = 53.7 kJ mol–1. DFT calculations agreed with an intrapyrazole proton transfer process assisted by two water molecules (ΔG = 63.1 kJ mol–1). An X-ray diffraction study on 4 indicated electron delocalization in the iridapyrazole ring. The reaction of the irida-β-diketone [IrHCl{(PPh2(o-C6H4CO))2H}] (1) with H2NNRR′ in aprotic solvents gave irida-β-ketoimines [IrHCl{(PPh2(o-C6H4CO))(PPh2(o-C6H4CNNRR′))H}] (R = R′ = Me (5); R = H, R′ = Ph (8)), which can undergo N–N bond cleavage to afford the acyl–amide complex [IrHCl(PPh2(o-C6H4CO))(PPh2(o-C6H4C(O)N(CH3)2))-κP,κO] (6) or [IrHCl(PPh2(o-C6H4CO))(PPh2(o-C6H4CN)-κP)(NH2NHPh-κNH2)] (9) containing o-(diphenylphosphine)benzonitrile and phenylhydrazine, respectively. From a CH2Cl2/CH3OH solution of 9 kept at −18 °C, single crystals of [IrHCl(PPh2(o-C6H4CO))(PPh2(o-C6H4CN)-κP))(HN═NPh-κNH)] (10) containing o-(diphenylphosphine)benzonitrile and phenyldiazene were formed, as shown by X-ray diffraction. The reaction of 1 with methylhydrazine in methanol gave the hydrazine complex [IrCl(PPh2(o-C6H4CO))2(NH2NH(CH3)-κNH2)] (7). Single-crystal X-ray diffraction analysis was performed on 6 and 7.Partial financial support by Ministerio de Economía y Competitividad (CTQ2015-65268-C2-1-P and CTQ2015-65268-C2-2-P), Gobierno Vasco (S-PE13UN023), and Universidad del País Vasco (UPV/EHU) (GIU 13/06) is gratefully acknowledged. I.Z. is grateful to Gobierno Vasco for a scholarship. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU, MICINN, GV/EJ, ERDF, and ESF) is gratefully acknowledged

Slow Magnetic Relaxation and Luminescent Properties of Mononuclear Lanthanide-Substituted Keggin-Type Polyoxotungstates with Compartmental Organic Ligands

This work was funded by Eusko Jaurlaritza/Gobierno Vasco (EJ/GV, grants IT1291-19 and KK-2020/00008) and Ministerio de Ciencia e Innovación (MCIN, grant MAT2017–89553-P). E.R.B. is indebted to EJ/GV for her predoctoral fellowship (PRE_2018_1_0143). E.C. thanks MCIN/AEI/10.13039/501100011033/ “FEDER Una manera de hacer Europa” (project PGC2018 102052-B-C21) and the I+D+i FEDER program 2018 of Junta de Andalucı́a (Project A-FQM-172-UGR18) for financial support.The reaction of mid to late lanthanide ions with the N,N′-dimethyl-N,N′-bis(2-hydroxy-3-formyl-5-bromobenzyl)ethylene-diamine organic ligand and monolacunary Keggin type [α-SiW11O39]8- anion affords a series of isostructural compounds, namely, K5[LnIII(α-SiW11O39)(C20H22Br2N2O4)]·14H2O (1-Ln, Ln = Sm to Lu). The molecular structure of these sandwich-type complexes is formed by the LnIII ion in a biaugmented trigonal prismatic geometry, which occupies the external O4 site of the organic ligand and the vacant site of the lacunary polyoxometalate (POM) unit. The empty N2O2 coordination site of the organic ligand allows its unprecedented folding, which displays a relative perpendicular arrangement of aromatic groups. Weak Br···Br and ?-πinteractions established between adjacent molecular units govern the crystal packing, which results in the formation of assemblies containing six hybrid species assembled in a chairlike conformation. 1-Gd and 1-Yb display slow relaxation of the magnetization after the application of an external magnetic field with maxima in the out-of-phase magnetic susceptibility plots below ?5-6 K, which is ascribed to the presence of various relaxation mechanisms. Moreover, photoluminescent emission is sensitized for 1-Sm and 1-Eu in the visible region and 1-Er and 1-Yb in the NIR. In contrast, the quenching of metal-centered luminescence in the 1-Tb derivative has been attributed to the out-of-pocket coordination mode of the lanthanide center within the POM fragment. It is demonstrated that the 1-Yb dual magneto-luminescent material represents the first lanthanide-containing POM reported to date with simultaneous slow magnetic relaxation and NIR emission. Solution stability of the hybrid molecular species in water is also confirmed by ESI-mass spectrometry experiments carried out for 1-Tb and 1-Tm.Eusko Jaurlaritza/Gobierno Vasco IT1291-19, KK-2020/00008I+D+i FEDER A-FQM-172-UGR18Ministerio de Ciencia e Innovación MAT2017–89553-P, PGC2018 102052-B-C2

Comparison of Figulla Flex® and Amplatzer™ devices for atrial septal defect closure: A meta-analysis

Background: Atrial septal defect (ASD) is one of the most common congenital heart diseases. Percutaneousclosure is the preferred treatment, but certain complications remain a concern. The most common devices are AMPLATZER™ (ASO) (St. Jude Medical, St. Paul, MN, USA) and Figulla Flex® septal occluders (FSO) (Occlutech GmbH, Jena, Germany). The present study aimed to assess main differences in outcomes.Methods: A systematic search in Pubmed and Google scholarship was performed by two independent reviewers for any study comparing ASO and FSO. Searched terms were “Figulla”, “Amplatzer”, and “atrial septal defect”. A random-effects model was used.Results: A total of 11 studies including 1770 patients (897 ASO; 873 FSO) were gathered. Baseline clinical and echocardiographic characteristics were comparable although septal aneurysm was more often reported in patients treated with ASO (32% vs. 25%; p = 0.061). Success rate (94% vs. 95%; OR: 0.81; 95% CI: 0.38–1.71; p = 0.58) and peri-procedural complications were comparable. Procedures were shorter, requiring less fluoroscopy time with an FSO device (OR: 0.59; 95% CI: 0.20–0.97; p = 0.003). Although the global rate of complications in long-term was similar, the ASO device was associated with a higher rate of supraventricular arrhythmias (14.7% vs. 7.8%, p = 0.009).Conclusions: Percutaneous closure of ASD is a safe and effective, irrespective of the type of device. No differences exist regarding procedural success between the ASO and FSO devices but the last was associated to shorter procedure time, less radiation, and lower rate of supraventricular arrhythmias in follow-up. Late cardiac perforation did not occur and death in the follow-up was exceptional

Association between cell-bound blood amyloid-β(1-40) levels and hippocampus volume

The identification of early, preferably presymptomatic, biomarkers and true etiologic factors for Alzheimer's disease (AD) is the first step toward establishing effective primary and secondary prevention programs. Consequently, the search for a relatively inexpensive and harmless biomarker for AD continues. Despite intensive research worldwide, to date there is no definitive plasma or blood biomarker indicating high or low risk of conversion to AD. Magnetic resonance imaging and β-amyloid (Aβ) levels in three blood compartments (diluted in plasma, undiluted in plasma and cell-bound) were measured in 96 subjects (33 with mild cognitive impairment, 14 with AD and 49 healthy controls). Pearson correlations were completed between 113 regions of interest (ROIs) (45 subcortical and 68 cortical) and Aβ levels. Pearson correlation analyses adjusted for the covariates age, sex, apolipoprotein E (ApoE), education and creatinine levels showed neuroimaging ROIs were associated with Aβ levels. Two statistical methods were applied to study the major relationships identified: (1) Pearson correlation with phenotype added as a covariate and (2) a meta-analysis stratified by phenotype. Neuroimaging data and plasma Aβ measurements were taken from 630 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects to be compared with our results. The left hippocampus was the brain region most correlated with Aβ(1-40) bound to blood cell pellets (partial correlation (pcor) = −0.37, P = 0.0007) after adjustment for the covariates age, gender and education, ApoE and creatinine levels. The correlation remained almost the same (pcor = −0.35, P = 0.002) if phenotype is also added as a covariate. The association between both measurements was independent of cognitive status. The left hemisphere entorhinal cortex also correlated with Aβ(1-40) cell-bound fraction. AB128 and ADNI plasma Aβ measurements were not related to any brain morphometric measurement. Association of cell-bound Aβ(1-40) in blood with left hippocampal volume was much stronger than previously observed in Aβ plasma fractions. If confirmed, this observation will require careful interpretation and must be taken into account for blood amyloid-based biomarker development