11 research outputs found

    Analysis of pregnancy-associated plasma protein a production in human adult cardiac progenitor cells

    Get PDF
    IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology

    Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

    Get PDF

    I Contratti di costa quali strumenti innovativi di gestione integrata delle zone costiere

    No full text
    This research is dedicated to the theme of integrated management of coastal zones and aims at showing the inadequacy of traditional administrative governance instruments in consideration of the human activities carried out on coastal zones, in comparison with innovative and partecipative governance models, such as coastal contracts. The protection and the sustainable management of coastal zones represents a matter of great concern that, since the 1980’s, has resulted in a different methodological approach to implement the sustainable development’s principle through the integrated of environmental, economic and social resources. The research analyses, at first, the traditional administrative instruments highlighting the condition of substantial separation between the typical sectors of maritime property management, urban planning and landscape discipline, and the fragmentation between statal, regional, and local competences and the implementation tools. This approach, as authoritatively observed, has so far produced disappointing results and the need to implement an organic protection action have prevailed, in line with the Protocol on Integrated Management of Mediterranean Coastal Areas. The Protocol requires a profound reconsideration of the coastal area, and a holistic approach to the issues of protection and sustanaible uses in coastal areas, overcoming the traditional administrative model articulated, as mentioned above, for separeted administrative areas. This new interdisciplinary approach is being implemented, relatively recently, through orderly, adaptive and participatory models, which stand side by side - without replacing - to the traditional planning tools of applicable urban planning. These tools are called "coastal contracts" and it will be the goal of this research to demonstrate their enormous potential as possible models for implementing local integrated coastal zone management policies

    Toxicity assessment of (99m)technetium-labeled human beta-defensin-3 in CD1 mice

    No full text
    Objective: Human beta-defensin-3 (HBD-3) is an antimicrobial peptide which is up-regulated during 99m inflammation. Based on the previously demonstrated capacity of technetium-99m ( Tc) labelled HBD-3 of distinguishing infection from inflammation in rats, we have decided to collect information on the potential toxicity of the tracer in view of its possible use for imaging in humans. Materials and Methods: 99m Recombinant HBD-3 underwent labeling with Tc. The CD1 mice were selected as standard rodent species. Ten mice, 5 male and 5 female, were subjected to physical examination and housed in a dedicated room in 5 per cage. After 9 days pre-test period, all mice were weighted for dose adjustment and received 99m intravenously 6mcg/mouse of Tc-HBD-3. Mortality was recorded daily, while body weight was registered once a week. Clinical observation of animals was performed daily for sickness symptoms due to 99m the drug treatment. At day 19 a second dose of 6mcg/mouse Tc-HBD-3, was administered. Twenty-four hours after the second dose (day 20) the animals were euthanized. A piece of liver, kidneys, heart and lungs was collected for histopathological analysis. Results:Our results showed that the labelled-HBD-3 dose did not induce significant toxicity in mice. Of course these parameters were not sufficient to authorize use in humans. This non-toxic dose of HBD-3 when translated from animals to humans resulted in an equivalent dose of approximately 25 times higher than that needed for imaging. Conclusion:Our non toxicity data of 99m using Tc-beta-defensin-3 in mice offer a further indication in favour of the clinical use of this radiopharmaceutical in all cases where discrimination between infection and inflammation is needed

    Labelling of Granulocytes by Phagocytic Engulfment with (64)Cu-Labelled Chitosan-Coated Magnetic Nanoparticles.

    No full text
    Purpose: The aim of the present work was to perform the labelling of granulocytes by theirengulfment with chitosan-coated magnetic 64Cu nanoparticles (MNPs) in order to obtain aradiopharmaceutical suitable for dual imaging (PET–MRI) of inflammatory/infective diseases.Procedures: Specimens of 5–20 mg MNPs were washed with saline–isotonic solution andrecuperated by magnetic decantation; assessment of the release of 64Cufrom labelled granulocytes in plasma was performed by measuring the radioactivity of both the cellularpellet and the supernatant solution.Results: Our data showed the binding capacity of chitosan-coated MNPs for cationic metal. Theamount of Cu+2 chelated captured per milligram of MNPs was constant and independent of thereagent concentrations. In all cases, more than 90% of the engulfed granulocytes were positiveto the TBE test. The MNPs were localised within the cells.Conclusion: In our in vitro model, MNPs are taken up by granulocytes through phagocytosis,whereas previously described methods were based on the use of a chelating agent that permitCu to cross the cell membrane. Moreover, the 64Cu-engulfed granulocytes showed a highstability of up to 80% of retained radioactivity after 24 h of incubation.; 10 mg MNPs wasallowed to reactwith 16 μg 64Cu [64Ni(p,n) at 12–9 MeV] followed by anion exchange chromatographywith a specific activity of 56 MBq/μg. Pellets of granulocytes were obtained from peripheral blood;MNPs engulfment by granulocytes was obtained and granulocyte-engulfed viability was assessed bythe trypan blue exclusion (TBE) test performed at 5 min, 2 h and 4 h; 15–58 μg Cu2+ (CuCl2·H2O) in 50 μl of acidified (pH 5.5)saline solution was added to the MNPs re-suspended saline–isotonic solutio

    Effect of External Magnetic Field on IV 99mTc-Labeled Aminosilane-Coated Iron Oxide Nanoparticles: Demonstration in a Rat Model: Special Report

    No full text
    ABSTRACT: Among the most interesting applications of ferromagnetic nanoparticles (NPs) in medicine is the potential for localizing pharmacologically or radioactively tagged agents directly to selected tissues selected by an adjustable external magnetic field. This concept is demonstrated by the application external magnetic field on IV Tc-labeled aminosilane-coated iron oxide NPs in a rat model. In a model comparing a rat with a 0.3-T magnet over a hind paw versus a rat without a magnet, a static acquisition at 45 minutes showed that 27% of the administered radioactivity was in the area subtended by the magnet, whereas the liver displays a percentage of binding of 14% in the presence of the magnet and of 16% in the absence of an external magnetic field. These preliminary results suggest that the application of an external magnetic field may be a viable route for the development of methods for the confinement of magnetic NPs labeled with radioactive isotopes targeted for predetermined sites of the body

    Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

    No full text
    Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors

    Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

    No full text
    Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship
    corecore