Migration of phthalates, alkylphenols, bisphenol A and di(2-ethylhexyl)adipate from food packaging

The migration of plastic components or additives from packaging to food can produce a risk for human health, in fact many of these plasticizers and additives are "Endocrine Distruptors", such as phthalates (PAEs), alkylphenols (APs), 2,2-bis(4-hydroxyphenyl)propane (bisphenol A or BPA) and di(2-ethylhexyl) adipate (DENA). The evaluation of some PAEs, some APs, BPA and DEHA levels in common food packaging (oil and natural tuna cans, marmalade cap, yogurt packaging, polystyrene dish, teat, bread bag, film, baby's bottle, aseptic plastic laminate paperboard carton and plastic wine top) was carried out by migration tests. Furthermore to evaluate the potential migration of plasticizers and additives from plastic wine tops, two extraction methods were used, one through incubation at 40 degrees C for 10 days and one by ultrasounds extraction. The simulants employed were distilled water, acetic acid at 3%, ethanol at 15% for wine top. The food simulant was extracted by solid phase extraction (SPE) and analyzed by GC-MS. Comparing these results with EU restrictions all samples showed contaminant migration lower than SML and OML established. Finally, about the comparison of two extraction methods, the extraction carried out for 10 days at 40 degrees C may be better than the other one in order to detect all compounds. (C) 2012 Elsevier Ltd. All rights reserved

Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells

Background: With the success of recent non-viral gene delivery-based COVID-19 vaccines, nanovectors have gained some public acceptance and come to the forefront of advanced therapies. Unfortunately, the relatively low ability of the vectors to overcome cellular barriers adversely affects their effectiveness. Scientists have thus been striving to develop ever more effective gene delivery vectors, but the results are still far from satisfactory. Therefore, developing novel strategies is probably the only way forward to bring about genuine change. Herein, we devise a brand-new gene delivery strategy to boost dramatically the transfection efficiency of two gold standard nucleic acid (NA)/polymer nanoparticles (polyplexes) in vitro. Results: We conceived a device to generate milli-to-nanoscale vibrational cues as a function of the frequency set, and deliver vertical uniaxial displacements to adherent cells in culture. A short-lived high-frequency vibrational load (t= 5 min, f= 1,000 Hz) caused abrupt and extensive plasmalemma outgrowths but was safe for cells as neither cell proliferation rate nor viability was affected. Cells took about 1 hr to revert to quasi-naIve morphology through plasma membrane remodeling. In turn, this eventually triggered the mechano-activated clathrin-mediated endocytic pathway and made cells more apt to internalize polyplexes, resulting in transfection efficiencies increased from 10-to100-fold. Noteworthy, these results were obtained transfecting three cell lines and hard-to-transfect primary cells. Conclusions: In this work, we focus on a new technology to enhance the intracellular delivery of NAs and improve the transfection efficiency of non-viral vectors through priming adherent cells with a short vibrational stimulation. This study paves the way for capitalizing on physical cell stimulation(s) to significantly raise the effectiveness of gene delivery vectors in vitro and ex vivo

Stellar photometry with Multi Conjugate Adaptive Optics

We overview the current status of photometric analyses of images collected with Multi Conjugate Adaptive Optics (MCAO) at 8-10m class telescopes that operated, or are operating, on sky. Particular attention will be payed to resolved stellar population studies. Stars in crowded stellar systems, such as globular clusters or in nearby galaxies, are ideal test particles to test AO performance. We will focus the discussion on photometric precision and accuracy reached nowadays. We briefly describe our project on stellar photometry and astrometry of Galactic globular clusters using images taken with GeMS at the Gemini South telescope. We also present the photometry performed with DAOPHOT suite of programs into the crowded regions of these globulars reaching very faint limiting magnitudes Ks ~21.5 mag on moderately large fields of view (~1.5 arcmin squared). We highlight the need for new algorithms to improve the modeling of the complex variation of the Point Spread Function across the field of view. Finally, we outline the role that large samples of stellar standards plays in providing a detailed description of the MCAO performance and in precise and accurate colour{magnitude diagrams.Comment: 17 pages, 12 figures, SPIE 201

Demineralized dentin and enamel matrices as suitable substrates for bone regeneration

Background: In recent decades, tooth derivatives such as dentin (D) and enamel (E) have been considered as potential graft biomaterials to treat bone defects. This study aimed to investigate the effects of demineralization on the physical-chemical and biological behavior of D and E. Methods: Human D and E were minced into particles (Ã\u98<1 mm), demineralized and sterilized. Thorough physicalchemical and biochemical characterizations of native and demineralized materials were performed by SEM and EDS analysis and ELISA kits to determine mineral, collagen type I and BMP-2 contents. In addition, MG63 and SAOS-2 cells were seeded on tooth-derived materials and Bio-Oss®, and a comparison of cell responses in terms of adhesion and proliferation was carried out. Results: The sterilization process, as a combination of chemical and thermal treatments, was found to be effective for all materials. On the other hand, D demineralization allowed preserving the collagen content, while increasing BMP-2 bioavailability. D and demineralized D (dD) displayed excellent biocompatibility, even greater than Bio-Oss®. Conversely, the high mineral content displayed by E, as confirmed by EDS analysis, inhibited cell proliferation. Of note, even though the demineralization process was somehow less effective in E than in D, demineralized E (dE) displayed increased BMP-2 bioavailability and improved performance in vitro compared with native E. Conclusions: Our results substantiate the idea that the demineralization process lead to an increase of BMP-2 bioavailability, thus paving the way toward development of more effective, osteoinductive tooth-derived materials for bone regeneration and replacement

BMP-2 and type I collagen preservation in human deciduous teeth after demineralization

Background: Great interest has recently been focused on tooth and tooth derivatives as suitable substrates for the treatment of alveolar bone defects. Here, we propose the use of demineralized baby teeth (BT) as potential grafting materials for bone augmentation procedures. Methods: Particles of human BT (Ø < 1 mm) were demineralized by means of a chemical/thermal treatment. Demineralized BT particles were thoroughly characterized by scanning electron microscopy/energy dispersive X-ray analyses to evaluate the effects of the demineralization on BT topography and mineral phase composition, and by enzyme-linked immunosorbent assays (ELISA) to quantify collagen and bone morphogenetic protein-2 (BMP-2) protein contents. The response of SAOS-2 cells to exogenous BMP-2 stimulation was evaluated to identify the minimum BMP-2 concentration able to induce osteodifferentiation in vitro (alkaline phosphatase (ALP) activity). Results: The demineralization treatment led to a dramatic decrease in relative Ca and P content (%) of ≈75% with respect to the native BT particles, while preserving native protein conformation and activity. Interestingly, the demineralization process led to a rise in the bioavailability of BMP-2 in BT particles, as compared to the untreated counterparts. The BMP-2 content found in demineralized BT was also proved to be very effective in enhancing ALP activity, thus in the osteodifferentiation of SAOS-2 cells in vitro, as confirmed by cell experiments performed upon exogenously added BMP-2. Conclusions: In this study we demonstrate that the BMP-2 content found in demineralized BT is very effective in inducing cell osteodifferentiation, and strengthens the idea that BTs are very attractive bioactive materials for bone-grafting procedures

Wireless Power Transfer Closed-Loop Control for Low-Power Active Implantable Medical Devices

Near-field resonant inductive coupling is the most mature wireless power transfer (WPT) method for implantable medical devices. Common commercial WPT components are not optimized neither to deliver small amounts of power nor to work with other than small air gaps. In this paper, a closed-loop control is integrated with commercial off-the-shelf WPT components to efficiently recharge and power an implantable device for controlled active drug delivery. The system keeps the transmitted power stable and reliable, achieving a 26 % transfer efficiency with delivered power of tens of milliwatts, guaranteeing an autonomy of 5 days with a 4-hour recharge. Overheating is kept around the 2 °C safety limit

Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

AbstractTaxane efficacy in triple negative breast cancer (TNBC) is limited by insufficient tumor accumulation and severe off-target effects. Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug. Here, 1,000 nm × 400 nm discoidal polymeric nanoconstructs (DPN) encapsulating docetaxel (DTXL) and the near infrared compound lipid-Cy5 were engineered. DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol) template with a polymer mixture comprising poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) diacrylate (PEG-DA) chains together with therapeutic and imaging agents. The resulting "multi-passage" DPN exhibited higher DTXL loading, lipid-Cy5 stability, and stiffness as compared to the conventional "single-passage" approach. Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof. Empty DPN had no toxicity on TNBC cells, whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL (IC50 = 2.6 nM ± 1.0 nM vs. 7.0 nM ± 1.09 nM at 72 h). In orthotopic murine models, DPN accumulated in TNBC more efficiently than free-DTXL. With only 2 mg/kg DTXL, intravenously administered every 2 days for a total of 13 treatments, DTXL-DPN induced tumor regression and were associated to an overall 80% survival rate as opposed to a 30% survival rate for free-DTXL, at 120 days. All untreated mice succumbed before 90 days. Collectively, this data demonstrates that vascular confined multi-passage DPN, biomimicking the behavior of circulating platelets, can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses

Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients

Purpose: Patients admitted to intensive care unit (ICU) with Klebsiella pneumoniae infections are characterized by high mortality. The aims of the present study were to investigate the population pharmacokinetics parameters and to assess the probability of target attainment of meropenem in critically ill patients to provide information for more effective regimens. Methods: Twenty-seven consecutive patients were included in the study. Meropenem was administered as 3-h intravenous (i.v.) infusions at doses of 1\u20132&nbsp;g every 8 or 12&nbsp;h. Meropenem plasma concentrations were measured by a high-performance liquid chromatography (HPLC) method, and a population pharmacokinetics analysis was performed using NONMEM software. Meropenem plasma disposition was simulated for extended (3&nbsp;h; 5&nbsp;h) or continuous i.v. infusions, and the following parameters were calculated: time during which free drug concentrations were above minimum inhibitory concentration (MIC) (fT&nbsp;&gt;&nbsp;MIC), free minimum plasma concentrations above 4 7 MIC (fCmin&nbsp;&gt;&nbsp;4 7 MIC), probability of target attainment (PTA), and cumulative fraction of response (CFR). Results: Gender and severity of sepsis affected meropenem clearance, whose typical population values ranged from 6.22 up to 12.04&nbsp;L/h (mean&nbsp;\ub1&nbsp;standard deviation (SD) value, 9.38&nbsp;\ub1&nbsp;4.47&nbsp;L/h). Mean Cmin value was 7.90&nbsp;\ub1&nbsp;7.91&nbsp;mg/L, suggesting a high interindividual variability. The simulation confirmed that 88 and 97.5&nbsp;% of patients achieved effective Cmin&nbsp;&gt;&nbsp;4 7 MIC values after 3- and 5-h i.v. infusions of meropenem 2&nbsp;g&nbsp; 7&nbsp;3/day, respectively. On the contrary, the same total daily doses reached the target Cmin&nbsp;&gt;&nbsp;4 7 MIC values in 100&nbsp;% of patients when administered as continuous i.v. infusions. Conclusions: Several factors may influence meropenem pharmacokinetics in ICU patients. Continuous i.v. infusions of meropenem seem to be more effective than standard regimens to achieve optimal therapeutic targets