Clinker based on calcium looped meals from the Cleanker Project.

The Cleanker (CLEAN clinKER production by Calcium Looping process) project, financed in the framework of Horizon 2020 EU funding program, has demonstrated the feasibility of the integrated CaL concept at industrial scale in a new demo system realised in the Buzzi Unicem cement plant in Vernasca (IT). The Calcium Looping (CaL) CO2 capture process exploits the reversible reaction of limestone calcination/carbonation (CaCO3 ↔ CaO + CO2). The Cleanker pilot plant consists of the coupling of a carbonator and an oxyfuel calciner. When the flue gases from kiln (containing CO2) flow through the carbonator together with calcined meal, which acts as a CO2 sorbent, carbonation takes place and CO2 is fixed in calcium carbonate. CaO is then regenerated in the calciner, where the opposite reaction takes place, and the captured CO2 is released. When the lime/limestone looping is carried out through a carbonator and a calciner operated in oxyfuel, a concentrated CO2 stream is obtained that can be efficiently addressed towards CCS or CCUS processes. In the Cleanker Project, the possibility to use raw meal for clinker production has been exploited and the meals sampled at the outlet of the oxyfuel calciner have been characterised and used for producing clinker at a lab scale. Calcium looped (CaL) meals collected at different sampling point during the operation of the CaL plant were characterised by means of X-ray fluorescence spectroscopy, X-ray diffraction and particle size distribution. Electron scanning microscopy revealed significant differences in the surface of particles of the looped meals with respect to the original one, resulting from the loading and unloading of CO2 during the looping cycles. The meals were burnt in a laboratory furnace and the obtained clinkers have been characterised on a chemical, mineralogical and microscopical point of view, revealing the good burnability of all the meals and attesting the possibility to reintegrate the materials in the clinker production process. A lower alite/belite ratio in the clinker produced from the looped meals was observed: actually, the depletion of calcium during the recirculation of the meal in the calciner/carbonator system led to a reduction of the lime saturation factor influencing the mineralogical composition of the product.

Cannabinoid Delivery Systems for Pain and Inflammation Treatment.

There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions. The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety. The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes. Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported.

Effect of prolonged refrigeration on the lipid profile, lipase activity, and oxidative status of human milk.

OBJECTIVE: The study was aimed at evaluating the effect of prolonged refrigeration of fresh human milk (HM) on its fatty acid profile, free fatty acid content, lipase activities, and oxidative status. METHODS: HM from mothers of preterm newborns was collected, pooled, and placed in the neonatal intensive care unit (NICU) refrigerator. Pooled milk was aliquoted and analyzed within 3 hours of collection, and after 24, 48, 72, and 96 hours of storage. The milk samples were analyzed for pH, total and free fatty acid profile, lipase activity at room temperature and at 4°C, lipase activity at room temperature in presence of sodium cholate (bile salt-dependent lipase), total antioxidant capacity, thiobarbituric acid reactive species, malondialdehyde, and conjugated diene concentration. The experiment was replicated in 3 independent trials. RESULTS: Prolonged refrigeration did not affect the fatty acid composition of breast milk, and preserved both its overall oxidative status and the activity of HM lipolytic enzymes. In particular, bile salt-dependent lipase activity, long-chain polyunsaturated fatty acids, and medium-chain saturated fatty acid concentrations were unaffected for up to 96 hours of refrigerated storage. CONCLUSIONS: Prolonged refrigeration of fresh HM for 96 hours maintained its overall lipid composition. The limited lipolysis during storage should be ascribed to the activity of lipoprotein lipase, responsible for the decrease in pH. Our study demonstrates that infants who receive expressed milk stored for up to 96 hours receive essentially the same supply of fatty acids and active lipases as do infants fed directly at the breast.

Qualitative characterization of Desmodium adscendens constituents by high-performance liquid chromatography-diode array ultraviolet-electrospray ionization multistage mass spectrometry.

The many effects of the African medicinal herb Desmodium adscendens were studied in the 1980s and 1990s. In spite of this, a comprehensive analytical protocol for the quality control of its constituents (soyasaponins, alkaloids and flavonoids) has not yet been formulated and reported. This study deals with the optimization of extraction conditions from the plant and qualitative identification of the constituents by HPLC-diode array UV and multistage mass spectrometry. Plant constituents were extracted from leaves by liquid-liquid and solid matrix dispersion extraction. Separation was achieved via RP-C18 liquid chromatographywith UV and MS(n) detection and mass spectrometry analysis was conducted by electrospray ionization ion trap or orbitrap mass spectrometry. High resolution mass spectrometry (HRMS) was used for structural identification of active molecules relating to soyasaponins and alkaloids. The flavonoid fragmentations were preliminarily studied by HRMS in order to accurately characterize the more common neutral losses. However, the high number of isomeric species induced us to make recourse to a more extended chromatographic separation in order to enable useful tandem mass spectrometry and ultraviolet spectral interpretation to propose a reasonable chemical classification of these polyphenols. 35 compounds of this class were identified herein with respect to the five reported in literature in this way we made up a comprehensive protocol for the qualitative analysis of the high complexity content of this plant. This result paves the way for both reliable quality control of potential phytochemical medicaments and possible future systematic clinical studies.

Characterization of alkaloids in bark extracts of Geissospermum vellosii by HPLC-UV-diode array-multistage high-resolution mass spectrometry.

A number of analytical studies, started in the sixties of the last century, concerning the stem bark of Geissospermum vellosii, have documented the presence of a number of indole alkaloids whose molecular identity was defined by NMR technique. The potential bioactivity of these compounds has inspired more recent analogous studies either devoted to structural elucidation of new alkaloid molecules or to the investigation of the role of some of them in cancer therapy. Anyway, a complete fingerprinting of the bark content is still lacking. In this paper, after a suitable extraction step, we obtain a chromatographic separation showing a number of components higher than the number of alkaloids so far described. Considering the great number of substances present in the stem bark, their identification is practically impossible to reveal by NMR techniques. As we presume that there are other stem bark unidentified alkaloids with important bioactivity, we propose to characterize their molecular structures by UV-Vis Diode Array spectrophotometry and High-Resolution Multistage Mass Spectrometry. The two adopted detection techniques were first tested on the already known Geissospermum vellosii molecules, and, after an inspection of their efficacy, were applied to the substances that have not yet been described. Herewith we propose the molecular structures of 10 substances that were never previously described, and in addition we provide experimental evidence of the presence of 6 already known substances which were never reported in the Geissospermum genus. A far more detailed description of the bark constituents is therefore provided.

Portland and Belite Cement Hydration Acceleration by C-S-H Seeds with Variable w/c Ratios.

The acceleration of very early age cement hydration by C-S-H seeding is getting attention from scholars and field applications because the enhanced early age features do not compromise later age performances. This acceleration could be beneficial for several low-CO2 cements as a general drawback is usually the low very early age mechanical strengths. However, the mechanistic understanding of this acceleration in commercial cements is not complete. Reported here is a contribution to this understanding from the study of the effects of C-S-H gel seeding in one Portland cement and two belite cements at two widely studied water-cement ratios, 0.50 and 0.40. Two commercially available C-S-H nano-seed-based admixtures, i.e., Master X-Seed 130 and Master X-Seed STE-53, were investigated. A multi-technique approach was adopted by employing calorimetry, thermal analysis, powder diffraction (data analysed by the Rietveld method), mercury intrusion porosimetry, and mechanical strength determination. For instance, the compressive strength at 1 day for the PC (w/c = 0.50) sample increased from 15 MPa for the unseeded mortar to 24 and 22 MPs for the mortars seeded with the XS130 and STE53, respectively. The evolution of the amorphous contents was determined by adding an internal standard before recording the powder patterns. In summary, alite and belite phase hydrations, from the crystalline phase content evolutions, are not significantly accelerated by C-S-H seedings at the studied ages of 1 and 28 d for these cements. Conversely, the hydration rates of tetracalcium alumino-ferrate and tricalcium aluminate were significantly enhanced. It is noted that the degrees of reaction of C4AF for the PC paste (w/c = 0.40) were 10, 30, and 40% at 1, 7, and 28 days. After C-S-H seeding, the values increased to 20, 45, and 60%, respectively. This resulted in larger ettringite contents at very early ages but not at 28 days. At 28 days of hydration, larger amounts of carbonate-containing AFm-type phases were determined. Finally, and importantly, the admixtures yielded larger amounts of amorphous components in the pastes at later hydration ages. This is justified, in part, by the higher content of amorphous iron siliceous hydrogarnet from the enhanced C4AF reactivity.

Strategies to expand the therapeutic potential of superoxide dismutase by exploiting delivery approaches.

The overproduction of free radicals can cause oxidative-stress damage to a range of biomolecules, and thus potentially contribute to several pathologies, from neurodegenerative disorders to cardiovascular diseases and metabolic disorders. Endogenous antioxidant enzymes, such as superoxide dismutase (SOD), play an important role in diminishing oxidative stress. SOD supplementation could therefore be an effective preventive strategy to reduce the risk of free-radical overproduction. However, the efficacy of SOD administration is hampered by its rapid clearance. Several different approaches to improve the bioavailability of SOD have been explored in recent decades. This review intends to describe the rationale that underlie the various approaches and chemical strategies that have led to the most recent advances in SOD delivery. This critical description includes SOD conjugates, SOD loaded into particulate carriers (micelles, liposomes, nanoparticles, microparticles) and the most promising and suitable formulations for oral delivery, with a particular emphasis on reports of preclinical/clinical results. Likely future directions are also considered and reported.

Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain.

The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients' quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations.

Multi-target detection of egg-white and pig gelatin fining agents in Nebbiolo-based aged red wine by means of nanoHPLC-HRMS.

The presence of residues from fining agents in wines may represent a risk for allergic consumers and a source of discomfort for others, such as vegans. Even though ELISA is the official detection method for such residues, this technique may be hindered by cross-reactivity issues, or by matrix-molecule interference due to a high polyphenol content, especially in red wines. An HRMS-based method has been developed to detect pig gelatin and egg white in experimental five-year aged Nebbiolo-based red wine. Biomarker peptides were selected, after tryptic digestion, and quantified by multitarget nanoHPLC-HRMS analysis. The method resulted in an LLOQs of 5 µg/mL in the experimental wine, and between 1 and 2 µg/mL in the buffer. This method allowed both gelatin and egg white proteins to be detected and quantified in aged red wine, while whereas the commercial ELISA kit was instead unable to detect egg white in the same samples.

Characterization and Determination of Interesterification Markers (Triacylglycerol Regioisomers) in Confectionery Oils by Liquid Chromatography-Mass Spectrometry.

Interesterification is an industrial transformation process aiming to change the physico-chemical properties of vegetable oils by redistributing fatty acid position within the original constituent of the triglycerides. In the confectionery industry, controlling formation degree of positional isomers is important in order to obtain fats with the desired properties. Silver ion HPLC (High Performance Liquid Chromatography) is the analytical technique usually adopted to separate triglycerides (TAGs) having different unsaturation degrees. However, separation of TAG positional isomers is a challenge when the number of double bonds is the same and the only difference is in their position within the triglyceride molecule. The TAG positional isomers involved in the present work have a structural specificity that require a separation method tailored to the needs of confectionery industry. The aim of this work was to obtain a chromatographic resolution that might allow reliable qualitative and quantitative evaluation of TAG positional isomers within reasonably rapid retention times and robust in respect of repeatability and reproducibility. The resulting analytical procedure was applied both to confectionery raw materials and final products.

Formation of by-products during chemical interesterification of lipids. Detection and characterization of dialkyl ketones by non-aqueous reversed-phase liquid chromatography-high resolution mass spectrometry and gas chromatography-mass spectrometry.

A new class of foreign substances present in the unsaponifiable fraction of vegetable oils undergone to chemical interesterification was systematically investigated. Their chemical structure, corresponding to dialkyl ketones (DAK) molecules, was elucidated both by gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-high resolution mass spectrometry (LC-HRMS). An analytical protocol aimed to qualitative and quantitative detection of DAK molecules in vegetable oils of confectionery industry interest was developed. Being the range of concentration levels to be evaluated dependent on the technological task of interesterification process, the quantitation step was thoroughly examined. All the validation parameters were satisfactory and particularly the concentration determinations were made more reliable by the contemporary use of several quantitation standards. GC-MS and LC-HRMS analytical techniques exhibited comparable performances even if the second one shown better detection sensitivity.

Nanostructured delivery systems with improved leishmanicidal activity: a critical review.

Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania, which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

Diagnosis of Louse-Borne Relapsing Fever despite Negative Microscopy in Two Asylum Seekers from Eastern Africa.

We report two cases of louse-borne relapsing fever observed at our Institution in June 2016. Both patients were young asylum seekers from Africa who had recently arrived in Milan, Italy. Notably, direct microscopic examination of peripheral blood smears was repeatedly negative for the presence of spirochetes and the diagnosis, supported by clinical and epidemiologic evidence, required molecular confirmation by polymerase chain reaction amplification of DNA extracted from blood and sequencing of the amplified products.

An experiment in the electrokinetic removal of copper from soil contaminated by the brass industry.

The feasibility of electrokinetic remediation of copper-contaminated soil was evaluated following eight days of electroreclamation. The results indicate that electrokinetic reclamation of Cu is totally ineffective in soil composed primarily of clay minerals and organic matter. The strong absorption of copper by this kind of soil, in our view mainly a result of retention by the clay component, makes it resistant to mobilization by the electrogenerated acidic front as well as by citrates (the competitors of natural chelating agents, i.e., humates). Such conditions, while adverse for the electroremediation process, may cause this kind of soil to act as a natural barrier to the leaching of copper ions.

Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase.

BACKGROUND: Increased superoxide production contributes to reduced vascular nitric oxide (NO) bioactivity and endothelial dysfunction in experimental models of diabetes. We characterized the sources and mechanisms underlying vascular superoxide production in human blood vessels from diabetic patients with coronary artery disease compared with nondiabetic patients. METHODS AND RESULTS: Vascular superoxide production was quantified in both saphenous veins and internal mammary arteries from 45 diabetic and 45 matched nondiabetic patients undergoing coronary artery bypass surgery. NAD(P)H-dependent oxidases were important sources of vascular superoxide in both diabetic and nondiabetic patients, but both the activity of this enzyme system and the levels of NAD(P)H oxidase protein subunits (p22phox, p67phox, and p47phox) were significantly increased in diabetic veins and arteries. In nondiabetic vessels, endothelial NO synthase produced NO that scavenged superoxide. However, in diabetic vessels, the endothelium was an additional net source of superoxide production because of dysfunctional endothelial NO synthase that was corrected by intracellular tetrahydrobiopterin supplementation. Furthermore, increased superoxide production in diabetes was abrogated by the protein kinase C inhibitor chelerythrine. CONCLUSIONS: These observations suggest important roles for NAD(P)H oxidases, endothelial NO synthase uncoupling, and protein kinase C signaling in mediating increased vascular superoxide production and endothelial dysfunction in human diabetes mellitus.

The early outcome in patients undergoing off-pump coronary artery bypass grafting: our experience.

BACKGROUND: Many studies confirm that beating heart surgery is an alternative to on-pump myocardial revascularization. However, the clinical conditions of patients are currently considered as a major landmark in the indication for beating heart surgery. This retrospective non-randomized study was carried out to evaluate the efficacy and the advantages of this surgical technique when anatomical criteria are used to choose the surgical strategy. METHODS: From February to December 2003, 222 consecutive patients underwent isolated myocardial revascularization: 76 (34%) with an off-pump coronary artery bypass (OPCAB) and 146 (66%) with an on-pump coronary artery bypass (ONCAB) procedure. Selection for surgical treatment was based on coronary anatomy. All patients were stratified for mortality risk class according to the EuroSCORE system. Operative and postoperative data were analyzed. RESULTS: Morbidity and mortality did not differ significantly between the two groups but the release of creatine kinase-MB fraction was significantly higher in the ONCAB group (48.7 +/- 55.3 vs 20.8 +/- 16.6 U/ml, p < 0.001). Patients at high surgical risk were dealt with a more complicated clinical outcome; logistic regression analysis showed that this class was an independent risk factor for postoperative complications in both groups. CONCLUSIONS: We did not find any statistical difference in hospital mortality and morbidity either using ONCAB or OPCAB; however a lower release of creatine kinase-MB in beating heart revascularization group suggests that OPCAB reduces myocardial injury and preserves cardiac function when anatomical criteria are considered for patient selection.

Analysis of regioisomers of polyunsaturated triacylglycerols in marine matrices by HPLC/HRMS.

Natural sources of triacylglycerols containing ω-3 fatty acids are of particular interest due to their protective role against several human diseases. However, as it has been well ascertained, the position of the ω-3 fatty acid on the triacylglycerol backbone influences how digestion occurs. In particular, occurrence at the sn-2 position allows optimal intestinal absorption conditions. The analytical protocol for regioisomer characterisation of fatty acids in a triacylglycerol usually requires the use of stereospecific lipases before instrumental identification. In this paper, we propose a more direct instrumental determination of triacylglycerol composition along with sn-2 positional identification of the fatty acids constituents by Liquid Chromatography-High Resolution Mass Spectrometry. Different intensities of product signals obtained in MS(2) and MS(3) experiments were used to define an interpretative scheme able to rationalise the stereochemistry of the TAGs. Marine matrices like tuna and algae oils have been studied in detail, their triacylglycerols identified and sn-2 positional arrangement of fatty acid constituents assessed.

Long-term follow-up of total arterial myocardial revascularization using exclusively pedicle bilateral internal thoracic artery and right gastroepiploic artery.

OBJECTIVE: In order to reduce remote cardiac events associated with graft occlusions, arterial conduits are being increasingly utilized in coronary artery bypass grafting (CABG). While the internal thoracic artery (ITA) is the graft of choice for CABG, it is sometimes difficult or impossible to obtain a complete arterial revascularization only with ITAs in three-vessel diseases. We present our experience with total arterial myocardial revascularization with bilateral internal thoracic artery (BITA) and right gastroepiploic artery (rGEA). METHODS: From April 1994 to January 2004, 174 patients (165 male, mean age 55.9+/-7.4) underwent coronary artery bypass procedure with exclusive use of BITA and rGEA. Left ventricular ejection fraction ranged from 20 to 68% (mean 55.9+/-6.8%). Seven patients (4%) had poor ejection fraction (<0.30), 23 (13, 2%) had acute myocardial infarction, 14 (8%) had left main disease. The mean CPB time was 96.9+/-15.7 min and the mean cross clamping time was 70+/-14.2 min. The mean number of distal anastomoses was 3.3+/-0.5 per patient. RESULTS: Early mortality was 1.7%. The patients were followed for up to 9 years (mean follow-up time 6.3+/-2.6 years). Actuarial freedom from cardiac death (including hospital death) was 97.6%, at 9 years after the operation. Actuarial freedom from angina and cardiac events at 9 years was 79, 5% and 77, 6%, respectively. No perioperative myocardial infarction occurred. None of the patients needed a redo-CABG after leaving the hospital. CONCLUSIONS: This study indicates that the myocardial revascularization in young patients with three-vessel disease using exclusively pedicle BITA and rGEA provides excellent 9-year patient survival and improvement in terms of freedom from return of angina pectoris and freedom from any cardiac-related event. These results encourage the more extensive use of BITA and rGEA in selected patients with three-vessel coronary disease.

Advances in anticancer antibody-drug conjugates and immunotoxins.

Antibody-delivered drugs and toxins are poised to become important classes of cancer therapeutics. These biopharmaceuticals have potential in this field, as they can selectively direct highly potent cytotoxic agents to cancer cells that present tumor-associated surface markers, thereby minimizing systemic toxicity. The activity of some conjugates is of particular interest receiving increasing attention, thanks to very promising clinical trial results in hematologic cancers. Over twenty antibody-drug conjugates and eight immunotoxins in clinical trials as well as some recently approved drugs, support the maturity of this approach. This review focuses on recent advances in the development of these two classes of biopharmaceuticals: conventional toxins and anticancer drugs, together with their mechanisms of action. The processes of conjugation and purification, as reported in the literature and in several patents, are discussed and the most relevant results in clinical trials are listed. Innovative technologies and preliminary results on novel drugs and toxins, as reported in the literature and in recently-published patents (up to February 2013) are lastly examined.

Detailed proteomic analysis on DM: insight into its hypoallergenicity.

Successful therapy in cow milk (CM) protein allergy rests upon completely eliminating CM proteins from the child's diet: it is thus necessary to provide a replacement food. Donkey milk (DM) has recently aroused scientific and clinical interest, above all among paediatric allergologists. A deeper knowledge of proteins in DM is necessary to evaluate the immunological and physiological properties of this natural substitute for cow's milk. The paper offers a detailed comparative analysis among the protein fractions of DM, CM and human milk, following an extensive proteomic study of the casein and whey proteins of DM performed by narrow pH range 2-DE. The detailed protein composition and structural features reported in this study provide insight into the molecular reasons for the hypoallergenicity of DM. Whole DM might constitute a valid substitute of CM in feeding children with CM protein allergy and it might also constitute the basis for formulas suitable for allergic subjects in the first year of life.