Praziquantel-loaded calcite crystals: Synthesis, physicochemical characterization, and biopharmaceutical properties of inorganic biomaterials for drug delivery

Drug delivery systems impacted significantly biomedical research, and the number of nano- and micro-formulations recently approved for clinical trials or marketed increased. Raw materials-based drug delivery systems have currently organic and inorganic origin, and calcium carbonate particles demonstrated several potentialities in biomedical applications and controlled drug delivery as well as they are safe and biocompatible. The aim of this study was the synthesis of calcium carbonate particles to improve the dissolution rate of praziquantel, a poorly water-soluble drug which is the gold standard for the treatment of parasite infections. Calcium carbonate particles were obtained using a synthetic carbon-based approach. Physicochemical properties of calcium carbonate particles, with or without praziquantel, were carried out by using scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray powder diffraction, thermal gravimetry and differential scanning calorimetry analysis. The solid-state characterization of calcium carbonate particles demonstrated that calcite crystals are synthesized, and these crystals interact specifically with praziquantel. The release profiles of praziquantel from calcium carbonate particles were further studied using United States Pharmacopeia dissolution test and the amount of drug released was quantified by using high performance liquid chromatography. Calcium carbonate particles increased the dissolution rate of praziquantel, which is higher than pure crystalline drug. Resulting data may suggest a potential application of these inorganic particles for oral and controlled release of praziquantel and their potential use as novel therapy for human helminthes infections.This work was financially supported by Ministero dell’Istruzione, dell’Università e della Ricerca [ FAR 2018 ( D56C18000780005 ), FAR 2019 ( D54I19002790005 )] to C. C. and L. D. M

LIGO/Virgo S200224ca: GRAWITA-Campo Imperatore observations

We carried out observations of the LIGO/Virgo trigger GW S200224ca (GCN Circ. #27184) using the INAF-OAAb 0.9m Schmidt Telescope of the INAF - Astronomical Observatory of Abruzzo located at 2150 meters o.s.l. at Campo Imperatore (Italy) and equipped with a 4096x4096 CCD covering a field of view of 1.15×1.15 square degrees. Due to weather conditions, only three pointings were made covering an area of nearly 4 square degrees; a containment probability of ~ 8 % of the 50% credible region was captured. The pointing sequence was generated using the GWsky script (G. Greco, https://github.com/ggreco77/GWsky), starting from the high probability region of the bayestar skymap and taking into account the airmass and relative density of nearby galaxies at the distance of 1585 +/- 331 Mpc. The total exposure time for each image was 3x180 sec. The observations were taken with the r-Sloan band on 2020-02-24 starting at 23:47:37.0 UT, about one hour after the GW detection (i.e. 2020-02-24 22:22:34.406 UTC). The estimated limiting magnitude in r-Sloan is about 21.5 mag. Hereafter the log of the observations. | RA (J2000) | Dec (J2000) | UT time | filter | exposure time| | 11:43:50.29 | -07:49:10 | 2020-02-24T23:47:37.0 | r-sloan | 3x180 sec | | 11:35:44.35 | -07:49:10 | 2020-02-25T00:04:09.6 | r-sloan | 3x180 sec | | 11:39:47.98 | -07:49:35 | 2020-02-25T00:20:44.8 | r-sloan | 3x180 sec | The analysis of images is ongoing. -------------------------------------------- De Luise Fiore, PhD INAF - Osservatorio Astronomico d'Abruzzo Via Mentore Maggini, s.n.c. 64100 - TERAMO Tel +39-0861-439712 Fax +39-0861-439740 -------------------------------------------

Dysbindin-1A modulation of astrocytic dopamine and basal ganglia dependent behaviors relevant to schizophrenia

The mechanisms underlying the dichotomic cortical/basal ganglia dopaminergic abnormalities in schizophrenia are unclear. Astrocytes are important non-neuronal modulators of brain circuits, but their role in dopaminergic system remains poorly explored. Microarray analyses, immunohistochemistry, and two-photon laser scanning microscopy revealed that Dys1 hypofunction increases the reactivity of astrocytes, which express only the Dys1A isoform. Notably, behavioral and electrochemical assessments in mice selectively lacking the Dys1A isoform unraveled a more prominent impact of Dys1A in behavioral and dopaminergic/D2 alterations related to basal ganglia, but not cortical functioning. Ex vivo electron microscopy and protein expression analyses indicated that selective Dys1A disruption might alter intracellular trafficking in astrocytes, but not in neurons. In agreement, Dys1A disruption only in astrocytes resulted in decreased motivation and sensorimotor gating deficits, increased astrocytic dopamine D2 receptors and decreased dopaminergic tone within basal ganglia. These processes might have clinical relevance because the caudate, but not the cortex, of patients with schizophrenia shows a reduction of the Dys1A isoform. Therefore, we started to show a hitherto unknown role for the Dys1A isoform in astrocytic-related modulation of basal ganglia behavioral and dopaminergic phenotypes, with relevance to schizophrenia

Community Branding (Co-Bra): A Collaborative Decision Making Process for Urban Regeneration

The paper introduces a methodology for a learning and negotiation process that supports urban regeneration, combining management models and multi-criteria/multi-group evaluation methods. The purpose concerns the urban regeneration issue in an interdisciplinary complex decisional context where Place Branding, Community Planning, Community Impact Evaluation, and Place Marketing interplay in a decision-making process named “Community Branding (Co-Bra)”. The processing of data and information elaborated by PROMETHEE (Preference Ranking Organisation METHod for Enrichment Evaluations) is crucial for providing the decision-maker with a ranking of alternatives based on preference degrees. Starting from the analysis carried out for Matera ECoC 2019, the case study of Pisticci (MT), the third-largest town in Basilicata (Italy), tested the methodological approach. The choice of a multidimensional approach, focused on the recognition of social, economic and cultural resources, provides strategies of enhancement of cultural heritage and community network by a “community hub”, called “PLUS – Pisticci Laboratorio Urbano Sostenibile” (Pisticci Sustainable Urban Lab)

Using Quality of Life Criteria to Define Urban Areas in Catalonia

Quality of life, Urban economics, Urban areas, Commuting algorithms, Gravitation models,

Elucidating the Formation of 6-Deoxyheptose: Biochemical Characterization of the GDP-d-glycero-d-manno-heptose C6 Dehydratase, DmhA, and Its Associated C4 Reductase, DmhB

6-Deoxyheptose is found within the surface polysaccharides of several bacterial pathogens. In Yersinia pseudotuberculosis, it is important for the barrier function of the O-antigen in vitro and for bacterial dissemination in vivo. The putative C6 dehydratase DmhA and C4 reductase DmhB, that were identified as responsible for 6-deoxyheptose synthesis based on genetics data, represent potential therapeutical targets. Their detailed biochemical characterization is presented herein. The substrate, GDP-D-glycero-D-manno-heptose, was synthesized enzymatically from sedoheptulose 7-phosphate using overexpressed and purified GmhA/B/C/D enzymes from Aneurinibacillus thermoaerophilus. Overexpressed and purified DmhA used this substrate with high efficiency, as indicated by its K(m) of 0.23 mM and k(cat) of 1.1 s(-1). The mass spectrometry (MS) analysis of the reaction product was consistent with a C6 dehydration reaction. DmhB could readily reduce this compound in the presence of NAD(P)H to produce GDP-6-deoxy-D-manno-heptose, as indicated by MS and NMR analyses. DmhA also used GDP-mannose as a substrate with a K(m) of 0.32 mM and a k(cat) of 0.25 min(-1). This kinetic analysis indicates that although the K(m) values for GDP-mannose and GDP-manno-heptose were similar, the genuine substrate for DmhA is GDP-manno-heptose. DmhB was also able to reduce the GDP-4-keto-6-deoxymannose produced by DmhA, although with poor efficiency and exclusively in the presence of NADPH. This study is the first complete biochemical characterization of the 6-deoxyheptose biosynthesis pathway. Also, it allows the screening for inhibitors, the elucidation of substrate specificity determinants, and the synthesis of carbohydrate antigens of therapeutic relevance