7 research outputs found
Peptide derivatives and therapeutic activity thereof
No full textDisclosed are peptide or pseudopeptide derivatives containing a nitrogenous heterocyclic residue with blocking activity against the by-products of lipid oxidative, stress, and in particular of unsaturated aldehydes such as malondialdehyde and 4-hydroxy-trans-2-nonenal (HNE). Formula (I
Frequency and anatomic variability of the mandibular lingual foramina : a cone-beam CT study
No full textBackground: To evaluate the distribution of lingual foramina (LF) and their correlation with demographic characteristics and mandible width, shape, and bone thickness in Caucasian Italian patients subjected to cone-beam CT (CBCT).
Methods: CBCTs were reviewed to assess the number of all LF, midline and lateral LF. We also assessed the relationship of the number of lateral LF with gender and mandibular width, shape, and bone thickness using the Chi Square test. A p value < 0.05 was considered statistically significant.
Results: Three-hundred patients (180 males; age range: 21-87 years) were included. The highest frequency per patient was of 2 LF (97/300, 32.3%), followed by 3 (81/300, 27%) and 4 (53/300, 17.7%). No LF were observed in 2/300 patients (0.7%), while the highest number was of 8 LF in one patient. The highest frequency of midline LF per person was of 2 LF (57.3%, 172/300), while the highest number per person was 5 LF in one patient (0.3%). The highest frequency of midline LF located above and below the genial tubercle was of 1 in 197/300 patients (65.7%) and in 169/300 patients (56.3%), respectively. Concerning lateral LF, the highest frequencies were of 0 (113/300, 37.7%) and of 1 (112/300, 37.3%). We did not observe any significant difference of the number of midline and lateral LF based on gender (P = .438 and P = .195, respectively) or mandible width (P = .069 and P = .114, respectively). The mandible shape was normal in 188 cases, with facial constriction in 42, lingual constriction in 54, and hour glass constriction in 16. The mean bone thickness was 10.76 mm in the symphysis, 10.92 mm in the right hemiarches, and 10.68 in the left hemiarches. No significant differences in the distribution of LF were observed also based on mandibular shape and bone thickness (both with P > .05).
Conclusions: We have shown the high variability of number and anatomic distribution of LF in an Italian group of patients subjected to CBCT without reporting any association with gender and mandible width, shape, and bone thickness
Novel quinuclidine derivatives to investigate the alpha-7 nicotinic acetylcholine receptor activation: new insight and perspectives
No full textThe homopentameric α7 nicotinic acetylcholine receptor (nAChR) belongs to the large cys-loop superfamily of neurotransmitter-gated ion channels and is widely expressed in neuronal cells, central and autonomic nervous system, and non-neuronal cells including immune cells, adipocytes, lung endothelial and epithelial cells. Given their widespread distribution and peculiar features, such as rapid channel activation and inactivation kinetics and high calcium permeability, the α7 nAChRs have been extensively investigated and appear to be implicated in central and peripheral diseases/pathological conditions, e.g. cognition disorders, schizophrenia, pain and inflammation. Growing findings suggest the involvement of α7 nAChRs in processes beyond their channel activity.1 Indeed, it has been proposed that they may mediate both channel activation-dependent and -independent forms of signaling.2,3 Recently, a direct coupling of the α7 nAChR to G proteins was hypothesized whereby its activation should be closely associated to the G protein intracellular signaling cycle, with the signal transduction being mediated through sites located in the well conserved α7 intracellular domain.4 The observation that some efficacious α7 anti-inflammatory modulators act as silent agonists, i.e. ligands which are unable to produce channel activation but can induce desensitized conformations of the receptor, seems to support these hypotheses.5
With the aim of further investigating the mechanisms of activation of the α7 nAChR, we designed, synthesized and tested novel spiro-Δ2-isoxazoline and methylene-1,2,4-oxadiazole derivatives connected to the quinuclidine ring, a structural moiety found in various α7 nAChR ligands (Figure 1).
Figure 1. Structures of the newly synthesized quinuclidine-containing nicotinic ligands.
The new derivatives were assayed in human α7 nAChRs expressed in Xenopus laevis oocytes by means of the two-electrode voltage clamping technique, applying a protocol developed by Papke et al.6 Interestingly, the biological data put in evidence a scaffold for the development of effective α7 nAChR silent agonists. Thus, our work could pave the way to a new class of α7 receptor activators endowed with a promising therapeutic potential
Novel 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazoles to investigate the activation of the α7 nicotinic acetylcholine receptor subtype: Synthesis and electrophysiological evaluation
No full textα7 nicotinic acetylcholine receptors (nAChRs) are relevant therapeutic targets for a variety of disorders including neurodegeneration, cognitive impairment, and inflammation. Although traditionally identified as an ionotropic receptor, the α7 subtype showed metabotropic-like functions, mainly linked to the modulation of immune responses. In the present work, we investigated the structure-activity relationships in a set of novel α7 ligands incorporating the 5-(quinuclidin-3-ylmethyl)-1,2,4-oxadiazole scaffold, i.e. derivatives 21a-34a and 21b-34b, aiming to identify the structural requirements able to preferentially trigger one of the two activation modes of this receptor subtype. The new compounds were characterized as partial and silent α7 nAChR agonists in electrophysiological assays, which allowed to assess the contribution of the different groups towards the final pharmacological profile. Overall, modifications of the selected structural backbone mainly afforded partial agonists, among them tertiary bases 27a-33a, whereas additional hydrogen-bond acceptor groups in permanently charged ligands, such as 29b and 31b, favored a silent desensitizing profile at the α7 nAChR
Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine-Δ2-Isoxazoline Scaffold : Synthesis and Electrophysiological Evaluation
No full textCompound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model compound for the design of new silent agonists of alpha7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little or no channel activation but can induce the alpha7 desensitized Ds state, which is sensitive to a type II positive allosteric modulator, such as PNU-120596. Introduction of meta substituents into the benzyloxy moiety of 11 led to two sets of tertiary amines and quaternary ammonium salts based on the spirocyclic quinuclidinyl-Delta2-isoxazoline scaffold. Electrophysiological assays performed on Xenopus laevis oocytes expressing human alpha7 nAChRs highlighted four compounds that are endowed with a significant silent-agonism profile. Structure-activity relationships of this group of analogues provided evidence of the crucial role of the positive charge at the quaternary quinuclidine nitrogen atom. Moreover, the present study indicates that meta substituents, in particular halogens, on the benzyloxy substructure direct specific interactions that stabilize a desensitized conformational state of the receptor and induce silent activity
Periapical status and technical quality in root canal filled teeth in a cross sectional study in Jönköping, Sweden
No full textObjectiveTo investigate the quality of root canal fillings and frequency of apical periodontitis (AP) in root canal filled teeth in a Swedish population.Material and methodsThis study used data from a cross-sectional survey conducted in 2013. The root canal filling quality and periapical status were assessed in 491 root canal filled teeth in 196 individuals aged 20-70 years, randomly selected from the population of Jonkoping, Sweden. All root canal filled teeth were examined with periapical radiographs. Three calibrated observers recorded length and density in root canal fillings as well as periapical status according to the Periapical Index. A root filling ending within 0.5-2 mm from the radiographic apex without lateral or apical voids was considered adequate. Data were analyzed in a generalized estimating equation (GEE) model with AP as dependent variable and gender, age, number of teeth, number of root filled teeth, tooth type, and root filling quality as independent variables.ResultsTeeth with technically inadequate root fillings were associated with AP in a simple GEE-analysis. In the multiple GEE-model, the association between technical quality and apical peridontitis was nonsignificant when controlling for tooth type and gender.ConclusionsThe quality of root canal fillings is poor and the prevalence of AP in root canal filled teeth is high, particularly in molar teeth, in a Swedish population.</p
Minerva in Colours: First Results on a Polychrome Roman Sculpture from Carnuntum (Pannonia)
No full textThis paper presents the first results of a current interdisciplinary research project on the polychromy of Roman provincial stone artefacts in selected areas of the Danubian provinces (PolychroMon). The statuary group of Minerva and the Genius immunium from Carnuntum (Archaeological Museum Carnuntinum inv. CAR-S-48) is dated to the second half of the second century AD and still retains traces of the original polychromy. The aim was to focus on non-invasive techniques and to employ micro-invasive methods for necessary cross-checking and gaining information otherwise not accessible. The investigation revealed that paint was applied on a layer of white lime wash. Additionally, the object shows several traces of Egyptian blue, which was mainly detected in Minerva’s and the Genius’ clothes. Other pigments whose traces were found on the sculpture include green earth, yellow and red ochre, as well as red lead and carbon black. Microscopic analysis confirms the presence of modern-age compounds as well (barium sulphate and zinc oxide) used for modern retouches. Gas chromatography–mass spectrometry revealed the use of egg as the major proteinaceous binding medium in the red lead polychromy
