169,897 research outputs found
Mechanochemical activation of Praziquantel in a vibrational mill
No full textThe research activity presented in this PhD thesis was totally dedicated to the application of mechanochemistry to Praziquantel using a vibrational mill, taking also advantage of the wide network of the group collaborators, both national and international. Praziquantel is an antihelmintic drug used worldwide against Schistosomiasis, which is a parasitic diseases affecting more than 200.000 people, especially in the sub-saharian area. Despite being highly effective and safe, this drug has 2 major drawbacks: the first one is the low biopharmaceutical profile (i.e. solubility and bioavailability) and therefore the high dosage needed. The second one is the very bitter and disgusting taste, which makes even more difficult its administration, in particular in pediatric patients, the main involved. The research started with the study of many co-ground systems of Praziquantel with different polymers used as pharmaceutical excipients, both at RT and under cryogenic conditions, to evaluate the process and formulation variables, obtaining amorphous dispersion with enhanced solubility and maintained antischistosomal activity (in vitro). Moreover, other binary systems were investigated: when using amorphous mesoporous silica, drug amorphisation was dramatically increased, even after only 15 minutes grinding, enhancing also drug dissolution and maintaining its in vitro antischistosomal activity. The grinding of Praziquantel with natural/synthetic sweeteners led to samples with enhanced solubility and intrinsic dissolution rate, possibly ameliorating also the drug taste. The neat grinding of the drug by itself led to the discovery of two new polymorphic forms, Form B and Form C, which structures were solved from the synchrotron X-Ray powder pattern and validated by DFT calculations. Form B was fully characterized, comprehending the in vitro and in vivo antischistosomal activity and the analysis of the pharmacokinetic profile. Form C, though exhibiting the higher solubility among the polymorphic forms, presented a poor physical stability of about 3 months. In addition, Form B and a cyo-coground sample were included in Gelucire 50/13 microparticles obtained via spray congealing, with a significative increase of drug solubility and dissolution rate. During the Erasmus period at the University of Cambridge, Praziquantel was subjected to Liquid-Assisted Grinding, discovering three new forms, one hemihydrate and two solvates respectively with Acetic Acid and 2-Pyrrolidone. The hemihydrate was fully characterized, both at the solid-state and from the biopharmaceutical point of view, including in vitro antischistosomal analysis, while the other forms are still under characterization. At the end, different sucrose esters were used both at the solid state and as aqueous solutions in combination with Praziquantel during grinding and Liquid-Assisted grinding
TOWARDS THE INTEGRATION OF MAGNETOTELLURIC WITH GEOLOGICAL SEISMIC AND GRAVITY DATA WITHIN THE SIRIPRO PROJECT
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Elevated HDL cholesterol levels: always beneficial?
No full textAn impressive number of studies published during the past years have demonstrated that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased cardiovascular risk. Nevertheless, more recent data in both ischemic heart disease patients and general population revealed that also considerably increased HDL-C concentration could be associated with enhanced risk of all-cause and cardiovascular mortality, displaying an U-shaped association with adverse outcomes. These paradoxical findings prompted us to review the available information on this matter, concluding that the association between extremely elevated HDL-C and mortality may not be totally unexpected or unpredictable. Some unfavorable consequences of high HDL-C levels are confirmed by epidemiologic data in over-trained subjects, in whom a similar U-shaped curve is also observed between strenuous training and mortality. This review is hence aimed to summarize these evidences, proffering some possible mechanisms underlying this enigmatic association. If this association could be confirmed in further studies, it may be advisable that laboratory reporting of HDL-C should encompass a range of “desirable values” rather than indicating a single lower decision threshold, as has been suggested until presently
The MEDRAP Concerted Action to support the Northern Mediterranean Action Programme to Combat Desertification
No full textEstrategias y acciones puestas en obra por el proyecto MEDRAP para sostener la redacción de un programa de acción regional para el Anexo IV Mediterraneo del norte
No full textThe role of grey water footprint in urban wastewater management: from pollution to reuse
No full textThe grey water footprint (WFgrey), defined as the volume of freshwater required to dilute pollutants below ambient water quality standards, has gained increasing relevance as a qualitative indicator of wastewater impact on receiving water bodies (RWB). This study evaluates the WFgrey using real data from a municipal wastewater treatment plant (WWTP) and its associated RWB over an eight-year period (2016–2023). A wide range of pollutants were considered, including organic compounds, solids, nutrients, and heavy metals. The analysis considered three scenarios: (a) untreated wastewater discharge, (b) treated effluent discharge, and (c) treated wastewater reuse for agricultural purposes. Results indicate that the WWTP significantly reduces pollutant loads, with scenario (b) showing an average 8-fold decrease in WFgrey compared to scenario
(a). Ammonium (in scenario (a)) and phosphorus (in scenario (b)) emerged as the primary contributors to WFgrey, highlighting the limited phosphorus removal due to the absence of dedicated chemical or biological treatments. Lead was found to be the most impactful heavy metal in several instances, underlining the importance of monitoring low-concentrated contaminants. Ammonium and total nitrogen showed the highest removal efficiency, whereas phosphorus removal was relatively inefficient, reinforcing the need for future plant upgrades. Furthermore, the reuse scenario (c) demonstrated the potential of nutrientrich treated effluent for irrigation, particularly during dry summer months, offering dual benefits of pollution reduction and resource recovery. Overall, WFgrey proved to be a robust and accessible indicator for evaluating WWTP performance,
identifying critical pollutants, guiding plant optimization, and supporting sustainable discharge and reuse strategies. Future developments should expand monitoring to emerging contaminants such as pharmaceuticals, pesticides, microplastics, and additional heavy metals to ensure comprehensive environmental protection
Distribution of CII and CIII peptides in lipoprotein classes: methods and clinical significance
No full textWe describe a method for measuring apolipoprotein (apo) C distribution between apo B-containing lipoprotein (apo B-LP) and non-apo B-LP. The procedure requires the precipitation of apo B-LP, the redissolution of the pellet, and the quantification of C peptides in the redissolved pellet. The ratio of apo C in non-apo B-LP to apo C in apo B-LP has been calculated for both CII and CII (R-CII and R-CIII, respectively). R-CII (0.49 +/- 0.25) and R-CIII (0.84 +/- 0.54) in patients on maintenance dialysis are significantly lower than in the control group (1.14 +/- 0.57 and 1.45 +/- 0.92, respectively), indicating that hypertriglyceridemia in these patients results from a reduced catabolism of triglyceride-rich LP (TGRLP). Patients with coronary artery disease (CAD) show a distribution of C peptides no different from the control group. Analysis of covariance reveals that the patterns of R-CII and R-CIII are not entirely predictable from the serum concentration of triglycerides. This result seems to support the hypothesis that the underlying metabolic defects involving TGRLP in dialysis patients are not the same as those in patients with CAD
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