Nanoparticles in the treatment of chronic lung diseases

Nanoparticles, although considered a topic of modern medicine, actually have an interesting history. Currently, advances in nanomedicine hold great promise as drug carrier systems for sustained release and targeted delivery of diverse therapeutic agents. Nanoparticles can be defined as complex drug carrier systems which incorporate and protect a certain drug or particle. Nanoparticles can be administered via different routes, such as intravenous injection, oral administration, or pulmonary inhalation. Even though the use of nano-carriers via pulmonary inhalation is heavily debated, this system represents an attractive alternative to the intravenous or oral routes, due to the unique anatomical and physiological features of the lungs and the minimal interactions between the targeted site and other organs. Some of the widely used nano-carriers for the treatment of chronic pulmonary diseases, via pulmonary route, are as follows: polymeric nanoparticles, liposomal nano-carriers, solid lipid nanoparticles, and submicron emulsions. Nano-carrier systems provide the advantage of sustained-drug release in the lung tissue resulting in reduced dosing frequency and improved patient compliance. Further studies focusing on understanding the mechanisms of action of nanoparticles and improving their chemical structure are required in order to better understand the potential long-term risk of excipient toxicity and nanoscale carriers

Large-scale numerical investigations of the antiferromagnetic Heisenberg icosidodecahedron

We present up to date investigations of the antiferromagnetic Heisenberg icosidodecahedron by means of the Density Matrix Renormalization Group method. We compare our results with modern Correlator Product State as well as Lanczos calculations.Comment: 20 pages, 11 figure

Effect of Binding Modules Fused to Cutinase on the Enzymatic Synthesis of Polyesters

open9In relation to the development of environmentally-friendly processing technologies for the continuously growing market of plastics, enzymes play an important role as green and sustainable biocatalysts. The present study reports the use of heterogeneous immobilized biocatalysts in solvent-free systems for the synthesis of aliphatic oligoesters with Mws and monomer conversions up to 1500 Da and 74%, respectively. To improve the accessibility of hydrophilic and hydrophobic substrates to the surface of the biocatalyst and improve the reaction kinetic and the chain elongation, two different binding modules were fused on the surface of cutinase 1 from Thermobifida cellulosilytica. The fusion enzymes were successfully immobilized (>99% of bound protein) via covalent bonding onto epoxy-activated beads. To the best of our knowledge, this is the first example where fused enzymes are used to catalyze transesterification reactions for polymer synthesis purposes.openFerrario, Valerio; Todea, Anamaria; Wolansky, Lisa; Piovesan, Nicola; Guarneri, Alice; Ribitsch, Doris; Guebitz, Georg M.; Gardossi, Lucia; Pellis, AlessandroFerrario, Valerio; Todea, Anamaria; Wolansky, Lisa; Piovesan, Nicola; Guarneri, Alice; Ribitsch, Doris; Guebitz, Georg M.; Gardossi, Lucia; Pellis, Alessandr

Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes.

Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes. Methods: Thirty-two RRMS patients (<5 years disease duration) underwent: (i) 3T MRI for CL/WML detection and clinical assessment at baseline and 2-years follow-up; and (ii) baseline blood test for sNfL. The correlation between the number and volume of CL/WML and sNfL was assessed by using the Spearman's rank correlation coefficient and a generalized linear model (GLM). A GLM was also used to assess the relationship between (i) the number/volume of new, enlarged, resolved, shrunken, stable lesions and (ii) the difference in clinical scores between two time-points. Results: At baseline, sNfL levels correlated with both total CL count/volume (ρ = 0.6/0.7, Corr-P <0.017/Corr-P < 0.001) and with total WML count/volume (ρ = 0.6/0.6, Corr-P < 0.01 for both). Baseline sNfL levels also correlated with new WML count/volume (ρ = 0.6/0.5, Corr-P < 0.01/Corr-P < 0.05) but not with new CL. Longitudinal changes in CL and WML count and volume were significantly associated with (i) sustained attention, auditory information, processing speed and flexibility (p < 0.01), (ii) verbal memory (p < 0.01); (iii) verbal fluency (p < 0.05); and (iv) hand-motor function (p < 0.05). Discussion: Changes in cortical and white matter focal damage in early MS patients correlate with global neuroaxonal damage and is associated to cognitive performances

Screening for Salt and Water Stress Tolerance in Fir (Abies alba) Populations

[EN] Drought periods are becoming more frequent and intense, due to the effects of climate change, threatening natural habitats worldwide, including European forests. Forest trees can also be affected by high soil salinity, because of the common practice of de-icing of mountain roads with NaCl in winter. We have evaluated the responses to salt and water stress of silver fir (Abies alba), an important forest species for which very limited information is available. One-year-old fir seedlings, with origin in seven different locations in Romania, were subjected to salt (watering with NaCl solutions of increasing concentrations) and water deficit (complete withholding of irrigation) treatments in the greenhouse. After one month, plant material was harvested and different morphological parameters were determined in the stressed and control plants. Both stress treatments inhibited growth of fir seedlings from all seven provenances, although quantitative differences in the responses to stress were observed between populations. Growth inhibition was established by the relative reduction ¿ as compared to the non-stressed controls - in several parameters, such as stem elongation, root length, number of needles, or fresh weight and water content of roots and needles. Statistical multivariate analysis of the results suggested that seedlings from Valea Morii (population 6) were the most tolerant to both, water deficit and high (300 mM NaCl) salt concentrations. These results support the possibility to screen a large number of individuals from different populations, at the seedling stage, to select Abies alba genotypes with enhanced drought and/or salinity tolerance.I.M.T.(M.) was recipients of Erasmus Mundus predoctoral scholarships in UPV financed by the European Commission.Todea (morar), IM.; González-Orenga, S.; Plazas Ávila, MDLO.; Sestras, AF.; Prohens Tomás, J.; Vicente, O.; Sestras, RE.... (2019). Screening for Salt and Water Stress Tolerance in Fir (Abies alba) Populations. Notulae Botanicae Horti Agrobotanici Cluj-Napoca. 47(4):1063-1072. https://doi.org/10.15835/nbha47411348S1063107247

Solid-State Characterization and Solubility

The authors acknowledge Fundac\u0327a\u0303o para a Cie\u0302ncia e a Tecnologia, and FEDER, Portugal 2020, and Lisboa 2020 for funding (project LISBOA-01-0145-FEDER-030988). Financial support is also acknowledged from grant POWR.03.02.00-00-I026/16 co-financed by the European Union through the European Social Fund under the Operational Program Knowledge Education Development and from Adam Mickiewicz University for the funds from the Initiative of Excellence Research University (ID-UB) program.This work is a contribution to the COST Action CA18112-Mechanochemistry for Sustainable Industry. Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.New cocrystals of praziquantel with suberic, 3-hydroxybenzoic, benzene-1,2,4,5-tetracarboxylic, trimesic, and 5-hydroxyisophthalic acids were obtained through ball milling experiments. The optimal conditions for the milling process were chosen by changing the solvent volume and the mechanical action time. Supramolecular interactions in the new cocrystals are detailed based on single-crystal X-ray diffraction analysis, confirming the expected formation of hydrogen bonds between the praziquantel carbonyl group and the carboxyl (or hydroxyl) moieties of the coformers. Different structural characterization techniques were performed for all samples, but the praziquantel:suberic acid cocrystal includes a wider range of investigations such as thermal analysis, infrared and X-ray photoelectron spectroscopies, and SEM microscopy. The stability for up to five months was established by keeping it under extreme conditions of temperature and humidity. Solubility studies were carried out for all the new forms disclosed herein and compared with the promising cocrystals previously reported with salicylic, 4-aminosalicylic, vanillic, and oxalic acids. HPLC analyses revealed a higher solubility for most of the new cocrystal forms, as compared to pure praziquantel.publishersversionpublishe

Calculating the energy spectra of magnetic molecules: application of real- and spin-space symmetries

The determination of the energy spectra of small spin systems as for instance given by magnetic molecules is a demanding numerical problem. In this work we review numerical approaches to diagonalize the Heisenberg Hamiltonian that employ symmetries; in particular we focus on the spin-rotational symmetry SU(2) in combination with point-group symmetries. With these methods one is able to block-diagonalize the Hamiltonian and thus to treat spin systems of unprecedented size. In addition it provides a spectroscopic labeling by irreducible representations that is helpful when interpreting transitions induced by Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance (NMR) or Inelastic Neutron Scattering (INS). It is our aim to provide the reader with detailed knowledge on how to set up such a diagonalization scheme.Comment: 29 pages, many figure

A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURO bservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

Aims: Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. Methods and results: We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (~20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA 2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. Conclusion: The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal. © The Author 2013