A serie of isostructural complexes with general formula M(ftpO)2(H2O)4 have been obtained from reaction between the first time characterized triazolopyrimidine derivative ...5-phenyl-1,2,4-triazolo1,5-apyrimidi-7(4H)-one (HftpO) (1) and first row transition nitrates (M=Cu (2), Co (3), Ni (4) and Zn (5)). A copper complex with formula Cu(HftpO)2(NO3)2(H2O)2·H2O (6) was also isolated. HftpO and their metal complexes have been characterized by spectroscopic and thermal analysis and their crystal structures have been solved by X-ray diffraction methods. The isostructural compounds are mononuclear complexes where the triazolopyrimidine ligand acts as monodentate ligand through N3 nitrogen position. The crystal structure of these novel bis-5-phenyl-1,2,4-triazolo1,5-apyrimidin-7(4H)-one-tetraaquo metal complexes offers an excellent opportunity at these complexes to acts as potential building blocks. Also, the antiparasitic activity of HftpO ligand against different leishmania and trypanosome strains has been studied.
Isostructural complexes with general formula M(ftpO)2(H2O)4 have been obtained from reaction between triazolopyrimidine derivative 5-phenyl-1,2,4-triazolo1,5-apyrimidi-7(4H)-one (HftpO) and first row transition nitrates. HftpO and their complexes have been characterized by spectroscopic and thermal analysis and X-ray diffraction. Antiparasitic activity of HftpO against Trypanosomatidae family strains has been studied. Display omitted
•New triazolopyrimidine derivative has been first time synthesized and characterized.•A serie of first row transition metal complexes have been synthesized and characterized.•Antiparasitic activity has been studied against leishmania and trypanosome strains.•Clearly superior efficacy in comparation with previous derivatives was demonstrate.
Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis ...with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.
We have built a vacuum double crystal spectrometer, which coupled to an electron-cyclotron resonance ion source, allows absolute measurements of low-energy X-ray transitions in highly charged ions ...with accuracies of the order of a few parts per million. We describe in detail the instrument and its performance. Furthermore, we present a few spectra of n=2→n=1 transitions in Ar14+, Ar15+ and Ar16+. We have developed an ab initio simulation code that allows us to obtain accurate line profiles. It can reproduce experimental spectra with unprecedented accuracy. The quality of the profiles allows the direct determination of line width.
•First use of a double crystal spectrometer to directly observe X-ray transitions in highly charged ions.•Accuracies of a few parts per million could be reached that provides test of quantum electrodynamics.•We have developed an ab initio simulation code that allows us to obtain accurate line profiles.•It can reproduce experimental spectra with unprecedented accuracy.•The details of the newly developed ab initio simulation code is presented.
Purpose Although body composition has emerged as an important predictor of drug efficacy and toxicity, explanations for this association are unclear. Our goal was to investigate relationships between ...lean body mass (LBM), liver size/function and epirubicin pharmacokinetics (PK) and toxicity. Methods Data from a clinical study (n = 24) of patients with breast cancer receiving adjuvant intravenous FE₁₀₀C chemotherapy were used to examine relationships between LBM, liver size, and epirubicin clearance. Muscle tissue and liver mass were measured by analysis of computerized tomography cross-sectional images, and an extrapolation of muscle mass to total LBM compartment was employed. Population PK analysis of epirubicin was undertaken to test effects of body composition on epirubicin clearance and area under the curve (AUC). Results Estimated LBM was extremely variable in this cohort ranging from 32.9 to 67.3 kg. LBM was associated with neutrophil nadir (r = 0.5, P = 0.023), and mean LBM was lower for patients presenting with toxicity compared to those where toxicity was absent (41.6 vs. 56.2 kg, P = 0.002); 33% of variance in clearance was explained by LBM and aspartate aminotransferase (AST). Liver mass was not related to epirubicin clearance likely due to larger livers presenting with larger fat content, but liver attenuation (degree of fat infiltration) and AST were associated with AUC. Conclusion To our knowledge, this is the first study to examine relationships between LBM, liver mass/function and epirubicin PK and toxicity. This exploratory work investigates the notion of organs and tissues having distinctive contributions to the distribution and metabolism of antineoplastic drugs.
The ligand and complexes were characterized by IR, UV- Visible ,1H NMR and elemental analysis, melting point, conductivity, metal ion intake and the antibacterial activity was studied. The ligand and ...complexes were characterized by IR, UV-visible H NMR and elemental analysis, melting point, conductivity; metal ion intake and antibacterial activity were studied. ...steric hindrance by the polymeric matrix and the hydrophobic nature of the polymeric ligand units can limit the chelating reaction (Tuncel et al., 2008). Canpolat, E., Yeiazi, A., and Kaya, M., Synthesis and Characterization of Mononuclear Cobalt(II), Nickel(II), Copper(II), Zinc(II), Cadmium(II) and Dinuclear Uranyl(VI) Complexes with N, N-bis (2{(2,2-dimethyl-1,3-dioxolan-4yl) methyl amino} butyl) N', N'dihydroxyethanediimidamide Transition Metal Chemistry. 2006; 31: 653-657.
Summary Objectives Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common ...determinants of outcome. Methods We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. Results The median age of participants was 64 years (interquartile range 50–75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). Conclusion The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus.
In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the ...understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca2+. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries.
Endoscopy related infections represent an important threat for healthcare systems worldwide. Recent outbreaks of infections with multidrug resistant micro-organisms have highlighted the problems of ...contaminated endoscopes. Endoscopes at highest risk for contamination have intricate mechanisms, multiple internal channels and narrow lumens that are especially problematic to clean. In light of raised awareness about the necessity for meticulous reprocessing of all types of endoscopes, a call for international collaboration is needed. An overview is presented on current practices for endoscope reprocessing in facilities worldwide.
An electronic survey was developed and disseminated by the International Society for Antimicrobials and Chemotherapy. The survey consisted of 50 questions aimed at assessing the reprocessing of flexible endoscopes internationally. It covered three core elements: stakeholder involvement, assessment of perceived risks, and reprocessing process.
The survey received a total of 165 completed responses from 39 countries. It is evident that most facilities, 82% (
= 136), have a standard operating procedure. There is, however a lot of variation within the flexible endoscope reprocessing practices observed. The need for regular training and education of reprocessing practitioners were identified by 50% (
= 83) of the respondents as main concerns that need to be addressed in order to increase patient safety in endoscope reprocessing procedures.
This international survey on current flexible endoscope reprocessing identified a large variation for reprocessing practices among different health care facilities/countries. A standardised education and training programme with a competency assessment is essential to prevent reprocessing lapses and improve patient safety.
PDF
