A series of fluorine substituted methoxyphenylalkyl amides were prepared with different orientations of the fluorine and methoxy groups with respect to the alkylamide side chain and with alkyl sides of differing lengths ( = 1-3). β-Dimethyl and α-methyl derivatives were also synthesised. The compounds were tested as melatonin agonists and antagonists using the pigment aggregation of melanophores as the biological assay.
View Article and Find Full Text PDFWe report the study of nanocomposite transparent electrodes based on aluminium doped zinc oxide (ZnO : Al) thin films and silver nanowire (AgNW) networks. The electrodes are fully fabricated by low-cost, open-air techniques, namely, atmospheric pressure spatial atomic layer deposition and spray coating. We show that the transparency and the electrical conductivity of the ZnO : Al/AgNW nanocomposites can be tuned by controlling the AgNW network density.
View Article and Find Full Text PDFThe synthesis and pharmacological evaluation of C1-substituted adamantane hydrazones, their C2-substituted isomers, and C1-substituted adamantane furanoic carboxamides is described. These new adamantane derivatives exhibited an interesting pharmacological profile in terms of trypanocidal activity and selectivity. The most active adduct with the best selectivity in this study was found to be the phenylacetoxy hydrazone 1 b (2-[4-(tricyclo[3.
View Article and Find Full Text PDFBone tumours around the elbow are rare. Even nowadays diagnostic dilemmas and delays are common. During recent decades the management and prognosis of patients with elbow bone tumours has improved significantly.
View Article and Find Full Text PDFHydrogen-deuterium exchange mass spectrometry (HDX-MS) is an established, powerful tool for investigating protein-ligand interactions, protein folding, and protein dynamics. However, HDX-MS is still an emergent tool for quality control of biopharmaceuticals and for establishing dynamic similarity between a biosimilar and an innovator therapeutic. Because industry will conduct quality control and similarity measurements over a product lifetime and in multiple locations, an understanding of HDX-MS reproducibility is critical.
View Article and Find Full Text PDFA new approach based on the uniform supersonic flow technique-a cold, thermalized de Laval expansion offering the advantage of performing experiments with condensable species-has been developed to study ion-molecule reactions at low temperatures. It employs a mass-selective radio frequency transfer line to capture and select ions from an adaptable ionization source and to inject the selected ions in the core of the supersonic expansion where rate coefficients and product branching can be measured from room temperature down to ∼15 K. The transfer line incorporates segmented ion guides combining quadrupolar and octapolar field orders to maximize transmission through the differential apertures and the large pressure gradients encountered between the ionization source (∼mbar), the quadrupole mass filter (∼10 mbar), and the de Laval expansion (∼mbar).
View Article and Find Full Text PDFIn this work, the synthesis and the pharmacological evaluation of diphenoxyadamantane alkylamines Ia-f and IIa-f is described. The new diphenoxy-substituted adamantanes share structural features present in trypanocidal and antitubercular agents. 1-Methylpiperazine derivative Ia is the most potent against T.
View Article and Find Full Text PDFHigh-frequency muscle tremor can mimic atrial flutter. Unnecessary therapies and aggressive interventions may have devastating consequences in these cases. We present a case of a patient with global pseudo-atrial flutter waves in the setting of essential tremor strictly confined to the arms.
View Article and Find Full Text PDFCost- and time-effective markers of Alzheimer's disease (AD), reliable and feasible at the population level are urgently needed. Soluble amyloid-β protein precursor β (sAβPPβ) in plasma has attracted scientific attention as a potential AD biomarker candidate. Here we report that plasma sAβPPβ levels in patients with AD dementia and typical for AD cerebrospinal fluid (CSF) biomarker profiles (N = 33) are significantly lower (p < 0.
View Article and Find Full Text PDFBackground: Oesophagectomy is associated with high morbidity and mortality rates. New-onset atrial fibrillation (AF) is a frequent complication following oesophagectomy. Several studies have explored whether new-onset AF is associated with adverse events after oesophagectomy.
View Article and Find Full Text PDFPhlebology
December 2019
Background: MitraClip device is a novel therapeutic option for patients with degenerative mitral valve regurgitation. Nevertheless, several studies have also focused on the safety and efficacy of this method in functional mitral valve regurgitation (FMR).
Aim: To systematically review all original studies that provided mortality data among FMR patients treated with MitraClip.
Hydrogen/deuterium exchange detected by mass spectrometry (HDXMS) provides valuable information on protein structure and dynamics. Although HDX-MS data is often interpreted using crystal structures, it was suggested that conformational ensembles produced by molecular dynamics simulations yield more accurate interpretations. In this paper, we analyse the complement protein C3d by performing an HDX-MS experiment, and evaluate several interpretation methodologies using an existing prediction model to derive HDX-MS data from protein structure.
View Article and Find Full Text PDFFeatures of intensive farming can seriously threaten pig homeostasis, well-being and productivity. Disease tolerance of an organism is the adaptive ability in preserving homeostasis and at the same time limiting the detrimental impact that infection can inflict on its health and performance without affecting pathogen burden . While disease resistance (DRs) can be assessed measuring appropriately the pathogen burden within the host, the tolerance cannot be quantified easily.
View Article and Find Full Text PDFBackground: To evaluate the effect of lumbar microdiscectomy (LM) in pain, disability and quality of life in a 5-year period and to identify potential demographic and clinical risk factors.
Methods: One hundred patients who underwent LM by the same surgeon participated in this prospective study. Clinical assessment was made with validated questionnaires preoperatively and up to 5 years postoperatively.
HuR is an abundant RNA-binding protein acting as a post-transcriptional regulator of many RNAs including mRNAs encoding inflammatory mediators, cytokines, death signalers and cell cycle regulators. In the context of intestinal pathologies, elevated HuR is considered to enhance the stability and the translation of pro-tumorigenic mRNAs providing the rationale for its pharmacological targeting. However, HuR also possesses specific regulatory functions for innate immunity and cytokine mRNA control which can oppose intestinal inflammation and tumor promotion.
View Article and Find Full Text PDFContrast Media Mol Imaging
July 2019
Background: Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate.
View Article and Find Full Text PDFMembers of the KDM5 histone H3 lysine 4 demethylase family are associated with therapeutic resistance, including endocrine resistance in breast cancer, but the underlying mechanism is poorly defined. Here we show that genetic deletion of KDM5A/B or inhibition of KDM5 activity increases sensitivity to anti-estrogens by modulating estrogen receptor (ER) signaling and by decreasing cellular transcriptomic heterogeneity. Higher KDM5B expression levels are associated with higher transcriptomic heterogeneity and poor prognosis in ER breast tumors.
View Article and Find Full Text PDFUpon ultraviolet activation, cannabinergic aliphatic azido (N) ligands covalently label cannabinoid receptors, prominent G-protein-coupled receptor (GPCR) drug targets. We report here the mechanism of covalent attachment to selected substrates of the high-affinity CBR inverse agonist AM1335 and its deuterated analog AM1335(d10), arylpyrazole compounds with an azide moiety at their n-pentyl side chain. To model the receptor interaction, we utilized the human cannabinoid 2 receptor (hCB2R) transmembrane helix 6 (TMH6) peptide and an N-acyl-protected cysteine (NAC).
View Article and Find Full Text PDFEur J Orthop Surg Traumatol
February 2019
Background: Lumbar microdiscectomy is a common procedure with satisfactory results; however, postoperative events like progressive adjacent level degeneration and perineural fibrosis can contribute to long-term pain. The purpose of the study was to evaluate MRI changes 5 years after lumbar microdiscectomy and assess their association with clinical parameters.
Materials And Methods: A prospective study enrolling 61 patients who underwent microdiscectomy.