Assessment of EtQxBox complexation in solution by steady-state and time-resolved fluorescence spectroscopy

Reliable chemical sensors with high selectivity and sensitivity toward specific target molecules require rational synthesis of receptors, in-depth characterization of their complexation abilities and highly efficient transduction of the molecular recognition event. Here we report a steady-state and time-resolved fluorescence investigation of EtQxBox, a fluorescent conformationally blocked quinoxaline-based cavitand, aimed at assessing its selectivity toward aromatic versus non-aromatic analytes in solution. Fluorescence quenching of the EtQxBox in acetone is observed at increasing concentration of both aromatic (i.e. benzonitrile) and aliphatic (i.e. acetonitrile) compounds. The combination with fluorescence lifetime measurements permits to discriminate the predominantly static quenching of the aromatic analyte, due to non-fluorescent host–guest complex formation, from the mostly dynamic quenching of the non-aromatic compound, resulting from aspecific diffusive collisions between the fluorophore and the quencher. The equilibrium association constants for both the complexes have been estimated using Stern–Volmer model.

We investigate the role of combined static and dynamic quenching in fluorescence transduction of benzonitrile and acetonitrile complexation by a rigid quinoxaline-based cavitand.     

Predictive factors for switching in patients with psoriatic arthritis undergoing anti-TNFα, anti-IL12/23, or anti-IL17 drugs: a 15-year monocentric real-life study

Clinical Rheumatology - We aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of...     

Chronic rejection after liver transplantation: Opening the Pandora’s box

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the “early” phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.     

Changes in the microvasculature with age

The microvasculature of various organs of the rat and of the mesentery of the cat were examined for histochemical changes as a function of age, using the periodic acid-Schiff (PAS) reaction. Arterioles, minute arteries, and nonmuscular venules were histochemically unchanged to approximately 17 months of age in the rat and 8 years in the cat. Subsequently, focal areas of PAS-positive material developed in the media of arterioles and small arteries and increased in extent and severity with age. The adventitia of nonmuscular venules normally stains slightly positive due to the mucopolysaccharide coating of collagen fibers. With age this adventitial layer becomes more intensely PAS-positive. In the 26-month-old rat and 19-year-old cat, the media of arterioles and small arteries were extensively hyalinized. Lesions of arteriosclerosis were not present. These observations, in consort with prior observations of others in various mammals, indicate that there is a regular systematic alteration of various elements of the microcirculation with age. A possible relationship between these anatomical changes and tissue exchange is considered.     

Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia

Intraduodenal lipid infusion induces symptoms and increases sensitivity to gastric distension in patients with functional dyspepsia. To test whether these effects are specific for lipid, we compared the effects of intraduodenal infusions of either lipid or glucose on symptoms and gastric sensory and motor responses to gastric distension. Eighteen dyspeptic patients and nine controls were studied. The stomach was distended with a flaccid bag during isocaloric infusions (1 kcal/ml) of saline and either 10% Intralipid (nine patients) or 26.7% glucose (nine patients) into the duodenum. Dyspeptic symptoms and sensory thresholds for epigastric fullness and discomfort were assessed. Gastric pressure profiles during distensions were similar during lipid and glucose infusions in patients and controls, but both were significantly lower than during saline infusion. Lower volumes were required to induce fullness and discomfort in the patients compared with the controls. In the controls, the threshold volumes required to induce fullness and discomfort were greater during infusion of lipid and glucose than during saline infusion, but in the patients, the threshold volumes were increased during glucose infusion but further reduced during lipid infusion. Moreover, in the patients, nausea was more common during lipid than glucose infusion and did not occur during saline. The controls did not experience any symptoms during any infusion. In conclusion, intraduodenal lipid but not glucose sensitizes the stomach to distension in patients with functional dyspepsia but not in controls.     

Evidence of vector-borne disease of Early Cretaceous reptiles

A blood-filled sand fly, Palaeomyia burmitis, was recently described from Early Cretaceous Burmese amber. Within the alimentary canal of this sand fly were the amastigotes and promastigotes of a digenetic leishmanial trypanosomatid. Inside the lumen of the thoracic midgut of the fossil sand fly were nucleated blood cells, some of which were intact and others in various stages of lysis and disintegration. The present study identifies these blood cells as reptilian and describes putative developing amastigotes inside spherical to oval whitish vacuoles within some of the fossil blood cells. The significance of this find is discussed, especially regarding the high possibility that Cretaceous dinosaurs were infected by trypanosomatids.