Synchronous Left Ventricular and Endocranial Mass.

Myocardial cysts represent a miscellaneous and infrequent spectrum of conditions, with each of them coming from a different etiological background. Congenital myocardial cysts, neoplasia, cysts of infectious origin (bacterial, viral, or parasitic), and cardiac pathologies that may fake cystic content are all encompassed in this group. Although most patients are asymptomatic, some may occasionally present with obstruction, valvular dysfunction, or heart failure. Even more uncommon is the coexistence of a myocardial cyst with other extracardiac locations causing extracardiac symptoms. In this direction, the coexistence of a myocardial and endocranial cyst is extremely rare and can cause symptomatology from the affected organs (e.g., seizures). Cardiac investigation in this context is mainly dependent on non-invasive diagnostic modalities, and laboratory procedures. In this case report, we present a 26-year-old Congolese male admitted with dyspnea and epileptic seizures. Echocardiography revealed left ventricular and both mitral and tricuspid valve dysfunction and the presence of two myocardial cysts, while brain computed tomography showed an additional frontal cystic lesion. A precise diagnostic workup with a combination of non-invasive imaging, laboratory results, and epidemiology data assisted the diagnosis and guided the most suitable therapeutic choice.

Branched Poly(ε-caprolactone)-Based Copolyesters of Different Architectures and Their Use in the Preparation of Anticancer Drug-Loaded Nanoparticles.

Limitations associated with the use of linear biodegradable polyesters in the preparation of anticancer nano-based drug delivery systems (nanoDDS) have turned scientific attention to the utilization of branched-chain (co-)polymers. In this context, the present study evaluates the use of novel branched poly(ε-caprolactone) (PCL)-based copolymers of different architectures for the preparation of anticancer nanoparticle (NP)-based formulations, using paclitaxel (PTX) as a model drug. Specifically, three PCL-polyol branched polyesters, namely, a three-arm copolymer based on glycerol (PCL-GLY), a four-arm copolymer based on pentaerythritol (PCL-PE), and a five-arm copolymer based on xylitol (PCL-XYL), were synthesized via ring-opening polymerization and characterized by proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography (GPC), intrinsic viscosity, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy and cytotoxicity. Then, PTX-loaded NPs were prepared by an oil-in-water emulsion. The size of the obtained NPs varied from 200 to 300 nm, while the drug was dispersed in crystalline form in all formulations. High encapsulation efficiency and high yields were obtained in all cases, while FTIR analysis showed no molecular drug polymer. Finally, in vitro drug release studies showed that the studied nanocarriers significantly enhanced the dissolution rate and extent of the drug.

Pegylated-polycaprolactone nano-sized drug delivery platforms loaded with biocompatible silver(i) complexes for anticancer therapeutics.

Cytotoxic potential of Ag(i) coordination compounds against cancer cells is widely recognized, but their frequently low water solubility and potential adverse interactions of Ag(i) ions in biological media require their incorporation into suitable platforms to ensure effective transport and delivery at target sites. Herein, we developed and evaluated the in vitro cytotoxic activity of a biodegradable copolymer-based nano-sized drug delivery system for three cytotoxically active and lipophillic Ag(i) compounds. In particular, polymer-based nanoparticles of the newly synthesized amphiphilic methoxy-poly(ethylene glycol)-poly(caprolactone) (mPEG-PCL) copolymer were prepared as carriers for [Ag(dmp2SH)(PPh3)2]NO3 (1), [Ag(dmp2SH)(xantphos)]NO3 (2) and [Ag(dmp2S)(xantphos)] (3) (dmP2SH = 4,6-dimethylpyrimidine-2-thiol, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) which exhibit high cytotoxicity against HeLa cancer cells, while they maintain low toxicity against HDFa normal cells. Taking advantage of the favorable donor-acceptor Lewis acid-base and electrostatic interactions between functional groups of 1-3 and mPEG-PCL copolymer, the formation of [X]@mPEG-PCL (X = 1,2,3) nanoparticles with nearly spherical shape was achieved. Satisfactory loading capacities and encapsulation efficiencies were obtained (13-15% and 80-88%, respectively). Differences in their mean size diameters were observed, revealing a dependence on the individual structural characteristics of the Ag(i) compounds. In vitro release profiles of the nanoparticles showed an initial burst stage, followed by a prolonged release stage extending over 15 days, with their release rates being determined by the mean size of the nanoparticles, as well as the type and crystallinity of the encapsulated Ag(i) compounds. In vitro cytotoxicity studies revealed an increased cytotoxic activity of compounds 1-3 after their encapsulation in mPEG-PCL copolymer against HeLa cells, with the actual concentrations of the loaded compounds responsible for the inhibition of cell viability being reduced by 8 times compared to the compounds in free form. Therefore, the current drug delivery system improves the pharmacokinetic properties of the three cytotoxic and biocompatible Ag(i) compounds, and may be beneficial for future in vivo anticancer treatment.

Dissolution Enhancement and Controlled Release of Paclitaxel Drug via a Hybrid Nanocarrier Based on mPEG-PCL Amphiphilic Copolymer and Fe-BTC Porous Metal-Organic Framework.

In the present work, the porous metal-organic framework (MOF) Basolite®F300 (Fe-BTC) was tested as a potential drug-releasing depot to enhance the solubility of the anticancer drug paclitaxel (PTX) and to prepare controlled release formulations after its encapsulation in amphiphilic methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) nanoparticles. Investigation revealed that drug adsorption in Fe-BTC reached approximately 40%, a relatively high level, and also led to an overall drug amorphization as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The dissolution rate of PTX-loaded MOF was substantially enhanced achieving a complete (100%) release within four days, while the neat drug only reached a 13% maximum rate (3-4 days). This PTX-Fe-BTC nanocomposite was further encapsulated into a mPEG-PCL matrix, a typical aliphatic amphiphilic copolyester synthesized in our lab, whose biocompatibility was validated by in vitro cytotoxicity tests toward human umbilical vein endothelial cells (HUVEC). Encapsulation was performed according to the solid-in-oil-in-water emulsion/solvent evaporation technique, resulting in nanoparticles of about 143 nm, slightly larger of those prepared without the pre-adsorption of PTX on Fe-BTC (138 nm, respectively). Transmission electron microscopy (TEM) imaging revealed that spherical nanoparticles with embedded PTX-loaded Fe-BTC nanoparticles were indeed fabricated, with sizes ranging from 80 to 150 nm. Regions of the composite Fe-BTC-PTX system in the infrared (IR) spectrum are identified as signatures of the drug-MOF interaction. The dissolution profiles of all nanoparticles showed an initial burst release, attributed to the drug amount located at the nanoparticles surface or close to it, followed by a steadily and controlled release. This is corroborated by computational analysis that reveals that PTX attaches effectively to Fe-BTC building blocks, but its relatively large size limits diffusion through crystalline regions of Fe-BTC. The dissolution behaviour can be described through a bimodal diffusivity model. The nanoparticles studied could serve as potential chemotherapeutic candidates for PTX delivery.

Formulation and In-Vitro Characterization of Chitosan-Nanoparticles Loaded with the Iron Chelator Deferoxamine Mesylate (DFO).

The objective of this study was to develop chitosan (CS) nanoparticles (NPs) loaded with deferoxamine mesylate (DFO) for slow release of this iron-chelating drug. Drug nanoencapsulation was performed via ionic gelation of chitosan using sodium tripolyphosphate (TPP) as cross-linker. Nanoparticles with a size ranging between 150 and 400 nm were prepared for neat CS/TPP with a 2/1 molar ratio while their yield was directly dependent on the applied stirring rate during the preparation process. DFO at different content (20, 45 and 75 wt %) was encapsulated into these nanoparticles. We found that drug loading correlates with increasing DFO content while the entrapment efficiency has an opposite behavior due to the high solubility of DFO. Hydrogen-bonding between amino and hydroxyl groups of DFO with reactive groups of CS were detected using FT-IR spectroscopy while X-ray diffraction revealed that DFO was entrapped in amorphous form in the CS nanoparticles. DFO release is directly dependent on the content of loaded drug, while model analysis revealed that the release mechanism of DFO for the CS/TPP nanoparticles is by diffusion. Treatment of murine RAW 264.7 macrophages with nanoencapsulated DFO promoted an increased expression of transferrin receptor 1 (TfR1) mRNA, a typical homeostatic response to iron deficiency. These data provide preliminary evidence for release of pharmacologically active DFO from the chitosan nanoparticles.

Effect of ion doping in silica-based nanoparticles on the hemolytic and oxidative activity in contact with human erythrocytes.

AIM: The aim of this study was the synthesis of ion doped silica-based nanoparticles and the evaluation of their toxic effect on erythrocytes. MATERIALS & METHODS: Their synthesis was performed using the sol-gel method, by the progressive addition of calcium, magnesium and copper ions on pure silica nanoparticles. The toxicity evaluation was based on hemolysis, lipid peroxidation, ROS, H2O2 species and antioxidant enzyme production. RESULTS: The addition of Mg and Cu in the SNs presented better hemocompatibility by protecting erythrocytes from oxidative stress. CONCLUSION: Ion doping with magnesium in the investigated calcium silicate system induces a protective effect in erythrocyte membrane in compare with pure silica nanoparticles.

Paclitaxel Magnetic Core⁻Shell Nanoparticles Based on Poly(lactic acid) Semitelechelic Novel Block Copolymers for Combined Hyperthermia and Chemotherapy Treatment of Cancer.

Magnetic hybrid inorganic/organic nanocarriers are promising alternatives for targeted cancer treatment. The present study evaluates the preparation of manganese ferrite magnetic nanoparticles (MnFe2O4 MNPs) encapsulated within Paclitaxel (PTX) loaded thioether-containing ω-hydroxyacid-co-poly(d,l-lactic acid) (TEHA-co-PDLLA) polymeric nanoparticles, for the combined hyperthermia and chemotherapy treatment of cancer. Initially, TEHA-co-PDLLA semitelechelic block copolymers were synthesized and characterized by 1H-NMR, FTIR, DSC, and XRD. FTIR analysis showed the formation of an ester bond between the two compounds, while DSC and XRD analysis showed that the prepared copolymers were amorphous. MnFe2O4 MNPs of relatively small crystallite size (12 nm) and moderate saturation magnetization (64 emu·g-1) were solvothermally synthesized in the sole presence of octadecylamine (ODA). PTX was amorphously dispersed within the polymeric matrix using emulsification/solvent evaporation method. Scanning electron microscopy along with energy-dispersive X-ray spectroscopy and transmission electron microscopy showed that the MnFe2O4 nanoparticles were effectively encapsulated within the drug-loaded polymeric nanoparticles. Dynamic light scattering measurements showed that the prepared nanoparticles had an average particle size of less than 160 nm with satisfactory yield and encapsulation efficiency. Diphasic PTX in vitro release over 18 days was observed while PTX dissolution rate was mainly controlled by the TEHA content. Finally, hyperthermia measurements and cytotoxicity studies were performed to evaluate the magnetic response, as well as the anticancer activity and the biocompatibility of the prepared nanocarriers.

Preparation of New Risperidone Depot Microspheres Based on Novel Biocompatible Poly(Alkylene Adipate) Polyesters as Long-Acting Injectable Formulations.

Risperidone (RIS)-loaded microspheres based on poly(alkylene adipate)s derived from dicarboxylic acids and different aliphatic diols were prepared by the oil in water emulsion and solvent evaporation method. Specifically, 3 polyesters, namely poly(ethylene adipate), poly(propylene adipate), and poly(butylene adipate), were prepared with the aid of a 2-stage melt-polycondensation method and characterized by gel permeation chromatography, proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry, and X-ray diffraction analysis. Results showed that the molecular weight of the polyesters increased as the diol molecular weight increased, while all polymers were of semi-crystalline nature and the melting temperature was varying from 49.1°C to 51.8°C and 65.9°C for poly(propylene adipate), poly(ethylene adipate), and poly(butylene adipate), respectively. The particle size of the RIS-loaded microspheres varied from 10 to 100 µm depending on the polyester type and the drug loading, while X-ray diffraction analysis revealed amorphous active pharmaceutical ingredient in the cases of high drug-loaded microspheres. In vitro drug release studies along with scanning electron microscopy images of microspheres after the completion of dissolution process showed that in all cases RIS release was controlled by the glass transition temperature of polyesters and physical state of active pharmaceutical ingredients via diffusion.

Epidemiology of acute coronary syndromes in the Mediterranean island of Cyprus (CYPACS study, Cyprus study of acute coronary syndromes).

INTRODUCTION: So far, no studies have been performed regarding the epidemiology and management of acute coronary syndromes (ACS) in Cyprus. The aim of the present study was to enroll a representative sample of patients in order to study the epidemiology and management of ACS in the Mediterranean island of Cyprus. METHODS: For a period of 12 months, all patients admitted to Nicosia General Hospital with an ACS were studied. The calculation of the annual incidence of ACS was based on the number of all ACS cases registered during one year in the Nicosia district. The results from the province of Nicosia can be considered as representative of the whole ACS profile in Cyprus. RESULTS: The annual incidence of ACS in the Nicosia district was 160 per 100,000 inhabitants (41 per 100,000 women and 282 per 100,000 men). This percentage translates into 1342 ACS episodes annually among the Cypriot population. The ratio of men to women was 6.8:1. More female ACS patients than men had hypertension (67.3% vs. 46.3%, p=0.005) and were passive smokers (53.8% vs. 47.7%, p=0.4), while male patients with ACS included a significantly greater percentage of smokers compared to women (51.3% vs. 13.5%, p<0.001). Regarding the type of ACS, 45% of patients were diagnosed with STEMI, 41.3% with NSTEMI and 13.7% with unstable angina. The majority of patients with STEMI were treated with medical reperfusion. The in-hospital mortality rate was 3.5%. CONCLUSIONS: The annual incidence of ACS in Cyprus is below the European average. The management of ACS is similar to that in southern Europe. The majority of patients with STEMI are treated with pharmacological reperfusion. The small geographical area of the island provides the advantage of early reperfusion to the majority of patients, which results in very low in-hospital mortality.