Doxorubicin and 4-nitrochalcone loaded in beeswax-based nanostructured lipid carriers: In vitro antitumoral screening and evaluation of synergistic effect on HepG-2 cells.

Cancer is the second most deadly disease worldwide, and the most traditional approaches such as chemotherapy still face limitations associated to drug dosage and off-target side effects. To address these issues, we propose the simultaneous administration of 4-Nitrochalcone (4NC) and Doxorubicin (DOX) using beeswax based nanostructured lipid carriers (NLCs). The co-encapsulation of 4NC and DOX in the beeswax based NLCs was performed using the water/oil/water double emulsion technique in association with the melt dispersion approach. The system composed by semi-spherical NLCs with an average diameter around 200 nm and narrow size distribution, displayed colloidal stability before and after redispersion, keeping the zeta potential below -30 mV. The antitumor activity of the nanoparticles was screened on different tumor cell lines, and the induced cellular death and internal ROS levels were analyzed on hepatocarcinoma cells, which were found to be more affected by the combination of 4NC and DOX. The results indicated that 4NC + DOX-NCLs could promote cytotoxicity and oxidative damage-mediated apoptosis in a HepG-2 cell line.

Identification of Potential New Aedes aegypti Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach.

Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA -265.95 ± 1.32 kJ/mol and -124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = -216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= -435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.

Biopolymer-based nanocarriers for sustained release of agrochemicals: A review on materials and social science perspectives for a sustainable future of agri- and horticulture.

Devastating plant diseases and soil depletion rationalize an extensive use of agrochemicals to secure the food production worldwide. The sustained release of fertilizers and pesticides in agriculture is a promising solution to the eco-toxicological impacts and it might reduce the amount and increase the effectiveness of agrochemicals administration in the field. This review article focusses on carriers with diameters below 1 µm, such as capsules, spheres, tubes and micelles that promote the sustained release of actives. Biopolymer nanocarriers represent a potentially environmentally friendly alternative due to their renewable origin and biodegradability, which prevents the formation of microplastics. The social aspects, economic potential, and success of commercialization of biopolymer based nanocarriers are influenced by the controversial nature of nanotechnology and depend on the use case. Nanotechnology's enormous innovative power is only able to unfold its potential to limit the effects of climate change and to counteract current environmental developments if the perceived risks are understood and mitigated.

Cellulose nanocarriers via miniemulsion allow Pathogen-Specific agrochemical delivery.

The current spraying of agrochemicals is unselective and ineffective, consuming a high amount of fungicides, which endangers the environment and human health. Cellulose-based nanocarriers (NCs) are a promising tool in sustainable agriculture and suitable vehicles for stimuli-responsive release of agrochemicals to target cellulase-segregating fungi, which cause severe plant diseases such as Apple Canker. Herein, cellulose was modified with undec-10-enoic acid to a hydrophobic and cross-linkable derivative, from which NCs were prepared via thiol-ene addition in miniemulsion. During the crosslinking reaction, the NCs were loaded in situ with hydrophobic fungicides, Captan and Pyraclostrobin. NCs with average sizes ranging from 200 to 300 nm and an agrochemical-load of 20 wt% were obtained. Cellulose-degrading fungi, e.g. Neonectria. ditissima which is responsible for Apple Canker, lead to the release of fungicides from the aqueous NC dispersions suppressing fungal growth. In contrast, the non-cellulase segregating fungi, e.g. Cylindrocladium buxicola, do not degrade the agrochemical-loaded NCs. This selective action against Apple Canker fungi, N. ditissima, proves the efficacy of NC-mediated drug delivery triggered by degradation in the exclusive presence of cellulolytic fungi. Cellulose NCs represent a sustainable alternative to the current unselective spraying of agrochemicals that treats many crop diseases ineffectively.

An Overview of the α4ß1 Integrin and the Potential Therapeutic Role of its Antagonists.

This article presents a simplified view of integrins with emphasis on the α4 (α4ß1/VLA-4) integrin. Integrins are heterodimeric proteins expressed on the cell surface of leukocytes that participate in a wide variety of functions, such as survival, growth, differentiation, migration, inflammatory responses, tumour invasion, among others. When the extracellular matrix is degraded or deformed, cells are forced to undergo responsive changes that influence remodelling during physiological and pathological events. Integrins recognize these changes and trigger a series of cellular responses, forming a physical connection between the interior and the outside of the cell. The communication of integrins through the plasma membrane occurs in both directions, from the extracellular to the intracellular (outside-in) and from the intracellular to the extracellular (inside-out). Integrins are valid targets for antibodies and small-molecule antagonists. One example is the monoclonal antibody natalizumab, marketed under the name of TYSABRI®, used in the treatment of recurrent multiple sclerosis, which inhibits the adhesion of α4 integrin to its counter-receptor. α4ß1 Integrin antagonists are summarized here, and their utility as therapeutics are also discussed.

Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches.

Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase-2 (COX-2) that were developed in order to avoid the side effects of non-selective inhibitors of COX-1. Thus, the present study aims to identify new selective chemical entities for the COX-2 enzyme via molecular modeling approaches. The best pharmacophore model was used to identify compounds within the ZINC database. The molecular properties were determined and selected with Pearson's correlation for the construction of quantitative structure-activity relationship (QSAR) models to predict the biological activities of the compounds obtained with virtual screening. The pharmacokinetic/toxicological profiles of the compounds were determined, as well as the binding modes through molecular docking compared to commercial compounds (rofecoxib and celecoxib). The QSAR analysis showed a fit with R = 0.9617, R2 = 0.9250, standard error of estimate (SEE) = 0.2238, and F = 46.2739, with the tetra-parametric regression model. After the analysis, only three promising inhibitors were selected, Z-964, Z-627, and Z-814, with their predicted pIC50 (-log IC50) values, Z-814 = 7.9484, Z-627 = 9.3458, and Z-964 = 9.5272. All candidates inhibitors complied with Lipinski's rule of five, which predicts a good oral availability and can be used in in vitro and in vivo tests in the zebrafish model in order to confirm the obtained in silico data.

Crosslinking of Electrospun Fibres from Unsaturated Polyesters by Bis-Triazolinediones (TAD).

Crosslinking of an unsaturated aliphatic polyester poly(globalide) (PGl) by bistriazolinediones (bisTADs) is reported. First, a monofunctional model compound, phenyl-TAD (PTAD), was tested for PGl functionalisation. 1H-NMR showed that PTAD-ene reaction was highly efficient with conversions up to 97%. Subsequently, hexamethylene bisTAD (HM-bisTAD) and methylene diphenyl bisTAD (MDP-bisTAD) were used to crosslink electrospun PGl fibres via one- and two-step approaches. In the one-step approach, PGl fibres were collected in a bisTAD solution for in situ crosslinking, which resulted in incomplete crosslinking. In the two-step approach, a light crosslinking of fibres was first achieved in a PGl non-solvent. Subsequent incubation in a fibre swelling bisTAD solution resulted in fully amorphous crosslinked fibres. SEM analysis revealed that the fibres' morphology was uncompromised by the crosslinking. A significant increase of tensile strength from 0.3 ± 0.08 MPa to 2.7 ± 0.8 MPa and 3.9 ± 0.5 MPa was observed when PGI fibres were crosslinked by HM-bisTAD and MDP-bisTAD, respectively. The reported methodology allows the design of electrospun fibres from biocompatible polyesters and the modulation of their mechanical and thermal properties. It also opens future opportunities for drug delivery applications by selected drug loading.

Catalytic Deoxygenation of the Oil and Biodiesel of Licuri (Syagrus coronata) To Obtain n-Alkanes with Chains in the Range of Biojet Fuels.

Aviation industry has the challenge of halving CO2 emissions by 2050, as compared to 2005. An alternative are drop-in biofuels, which are sustainable and fully compatible with aircraft engines and also can be mixed with fossil jet fuel. Among the feedstock for biojet fuel production, licuri (Syagrus coronata) can be highlighted as most of its fatty acids are in the jet fuel range. Thereby, this work investigated the composition and physicochemical characterization of licuri oil and licuri biodiesel, both with satisfactory results according to international standards, with the purpose of obtaining hydrocarbons in the range of jet fuel from these feedstock, by catalytic deoxygenation. The semi-batch reaction, using a 5% Pd/C catalyst at 300 °C and 207 psi, produced n-alkanes with a conversion of up to 39.2%. The n-alkane selectivity was 80.7%, in addition to CO2 selectivity of 83.4% for biodiesel, indicating the preference for the decarboxylation pathway and also confirming licuri as a potential raw material for biojet fuel.

Covalently Binding of Bovine Serum Albumin to Unsaturated Poly(Globalide-Co-ε-Caprolactone) Nanoparticles by Thiol-Ene Reactions.

When nanoparticles (NPs) are introduced to a biological fluid, different proteins (and other biomolecules) rapidly get adsorbed onto their surface, forming a protein corona capable of giving to the NPs a new "identity" and determine their biological fate. Protein-nanoparticle conjugation can be used in order to promote specific interactions between living systems and nanocarriers. Non-covalent conjugates are less stable and more susceptible to desorption in biological media, which makes the development of engineered nanoparticle surfaces by covalent attachment an interesting topic. In this work, the surface of poly(globalide-co-ε-caprolactone) (PGlCL) nanoparticles containing double bonds in the main polymer chain is covalently functionalized with bovine serum albumin (BSA) by thiol-ene chemistry, producing conjugates which are resistant to dissociation. The successful formation of the covalent conjugates is confirmed by flow cytometry (FC) and fluorescence correlation spectroscopy (FCS). Transmission electron microscopy (TEM) allows the visualization of the conjugate formation, and the presence of a protein layer surrounding the NPs can be observed. After conjugation with BSA, NPs present reduced cell uptake by HeLa and macrophage RAW264.7 cells, in comparison to uncoated NP. These results demonstrate that it is possible to produce stable conjugates by covalently binding BSA to PGlCL NP through thiol-ene reaction.

Diethyldithiocarbamate loaded in beeswax-copaiba oil nanoparticles obtained by solventless double emulsion technique promote promastigote death in vitro.

Leishmaniasis is considered a neglected tropical disease that represents a Public Health problem due to its high incidence. In the search of new alternatives for Leishmaniasis treatment diethyldithiocarbamate (DETC) has shown an excellent leishmanicidal activity and the incorporation into drug carrier systems, such as solid lipid nanoparticles (SLNs), is very promising. In the present work DETC loaded in beeswax nanoparticles containing copaiba oil were obtained by the double emulsion/melt technique. The nanoparticles were characterized and leishmanicidal activity against L. amazonensis promastigotes forms and cytotoxicity in murine macrophages were evaluated. SLNs presented size below 200 nm, spherical morphology, negative charge surface, high encapsulation efficiency, above 80%, and excellent stability. Moreover, Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses were performed to evaluate the chemical structure and possible interactions between DETC and SLNs. SLNs provided a protection for DETC, decreasing its cytotoxic effects in macrophages, which led to an improvement in the selectivity against the parasites, which almost doubled from free DETC (11.4) to DETC incorporated in SLNs (18.2). These results demonstrated that SLNs had a direct effect on L. amazonensis promastigotes without affect the viability of macrophage cell, can be a promising alternative therapy for the cutaneous treatment of L. amazonensis.

Synthesis of a green polyurethane foam from a biopolyol obtained by enzymatic glycerolysis and its use for immobilization of lipase NS-40116.

The use of green sources for materials synthesis has gained popularity in recent years. This work investigated the immobilization of lipase NS-40116 (Thermomyces lanuginosus lipase) in polyurethane foam (PUF) using a biopolyol obtained through the enzymatic glycerolysis between castor oil and glycerol, catalyzed by the commercial lipase Novozym 435 for the PUF formation. The reaction was performed to obtain biopolyol resulting in the conversion of 64% in mono- and diacylglycerol, promoting the efficient use of the reaction product as biopolyol to obtain polyurethane foam. The enzymatic derivative with immobilized lipase NS-40116 presented apparent density of 0.19 ± 0.03 g/cm3 and an immobilization yield was 94 ± 4%. Free and immobilized lipase NS-40116 were characterized in different solvents (methanol, ethanol, and propanol), temperatures (20, 40, 60 and 80 °C), pH (3, 5, 7, 9 and 11) and presence of ions Na+, Mg++, and Ca++. The support provided higher stability to the enzyme, mainly when subjected to acid pH (free lipase lost 80% of relative activity after 360 h of contact, when the enzymatic derivative lost around 22%) and high-temperature free lipase lost 50% of relative activity, while the immobilized remained 95%. The enzymatic derivative was also used for esterification reactions and conversions around 66% in fatty acid methyl esters, using abdominal chicken fat as feedstock, were obtained in the first use, maintaining this high conversion until the fourth reuse, proving that the support obtained using environmentally friendly techniques is applicable.

N-acetylcysteine side-chain functionalization of poly(globalide-co-ε-caprolactone) through thiol-ene reaction.

N-Acetylcysteine (NAC) is a drug well known for its antimucolytic action, antioxidant activity and ability to protect cells from oxidative stress. Conjugation of NAC with double bonds in the main polymer chain of poly(globalide-co-ε-caprolactone) (PGlCL) through thiol-ene reaction is reported. Different globalide (Gl) (an unsaturated macrolactone) to ε-caprolactone (CL) ratios were employed for PGlCL synthesis. The polymeric materials (PGlCL-NAC) were evaluated in terms of the number of functionalized double bonds, thermal properties, affinity for water and antioxidant potential. PGlCL-NAC containing more globalide repeating units presented higher degree of functionalization, due to the higher number of double bonds available to react through thiol-ene coupling. For high globalide contents (Gl/CL ratios above 50/50), NAC coupling in PGlCL chains resulted in completely amorphous copolymers with a more hydrophilic character, which should enhance bioresorption and cell adhesion characteristics. Functionalization also gave rise to a thioether linkage, conferring to PGlCL-NAC an antioxidant character, important for biomedical applications, where the material could combat cellular oxidative-stress.

Role of Lock Therapy for Long-Term Catheter-Related Infections by Multidrug-Resistant Bacteria.

The management of long-term central venous catheter (LTCVC) infections by multidrug-resistant (MDR) bacteria in cancer patient is a challenge. The objectives of this study were to analyze outcomes in cancer patients with LTCVC-associated infection, identify risks for unfavorable outcomes, and determine the impact of MDR bacteria and antibiotic lock therapy (ALT) in managing such infections. We evaluated all LTCVC-associated infections treated between January 2009 and December 2016. Infections were reported in accordance with international guidelines for catheter-related infections. The outcome measures were 30-day mortality and treatment failure. We analyzed risk factors by Cox forward-stepwise regression. We identified 296 LTCVC-associated infections; 212 (71.6%) were classified as bloodstream infections (BSIs). The most common agent was Staphylococcus aureus Forty-six (21.7%) infections were due to MDR Gram-negative bacteria. ALT was used in 62 (29.2%) patients, with a 75.9% success rate. Risk factors identified for failure of the initial treatment were having a high sequential organ failure assessment (SOFA) score at diagnosis of infection and being in palliative care; introduction of ALT at the start of treatment was identified as a protective factor. Risk factors identified for 30-day mortality after LTCVC-associated infection were a high SOFA score at diagnosis, infection with MDR bacteria, and palliative care; introduction of ALT at the start of treatment, hematological malignancies, and adherence to an institutional protocol for the management of LTCVC-associated infection were identified as protective factors. Despite the high incidence of infection with MDR bacteria, ALT improves the outcome of LTCVC-associated infection in cancer patients.

What happens to the pleural space affected by malignant effusion after bedside pleurodesis?

BACKGROUND AND OBJECTIVES: Evaluate radiological characteristics of postpleurodesis pleural space of patients with recurrent malignant pleural effusion(RMPE). METHODS: Prospective cohort study including patients with RPME treated with bedside pleurodesis. We used CT scans to calculate pleural cavity volume immediately before pleurodesis(iCT) and 30 days after(CT30). Radiological evolution was calculated by the difference between pleural volumes on CT30 and iCT(Δvolume). We categorized initial pleural volume as small(<500 mL) or large space(≥500 mL) and Δvolume as positive(>254.49 mL), unchanged(≥-268.77-≤ 254.49 mL), or negative(<-268.77 mL). Futhermore, we analyzed clinical effectiveness, pleural elastance, and adverse events. RESULTS: A total of 87 patients were analyzed. Pleural volume varied from 35-2750 mL in iCT and from 0-2995 mL in CT30(P = 0.753). A total of 54 patients had initial small pleural space(62.06%) and 33 large(37.93%). Clinical failure occurred in 7.4% of small space group and in 24.6% of large(P = 0.051, OR4.0(CI:1.098-14.570)). In small space group, 27.77% evolved with positive, 66.66% with unchanged and 5.55% with negative Δvolume. In the large space group these numbers were respectively 21.21%, 27.27%, and 51.51%. CONCLUSIONS: There is significant variability on pleural space volume. However, pleural volume remains unchanged in many cases. Besides that, more than half patients with initial large space coursed with relevant reduction. Finally, patients with initial small space presented a greater chance of clinical success.

Thiol-ene miniemulsion polymerization of a biobased monomer for biomedical applications.

Herein, we present the synthesis and characterization of poly(thioether-ester) nanoparticles via thiol-ene miniemulsion polymerization using a biobased α,ω-diene diester monomer, namely dianhydro-d-glucityl diundec-10-enoate (DGU), synthesized from 10-undecenoic acid (derived from castor oil) and isosorbide (derived from starch). DGU was copolymerized with 1,4-butanedithiol by thiol-ene miniemulsion polymerization resulting in waterborne poly(thioether-ester) particles with diameter around 200nm. Polymers with number average molecular weight up to 11kDa were obtained via miniemulsion polymerization. DSC and XRD analyses indicated a semi-crystalline polymer with a degree of crystallinity of at least 20% and Tm around 68°C. In addition, Coumarin 6 was encapsulated in the polymer particles with efficiency up to 98%. Nanoparticles presented biocompatibility in murine fibroblast (L929) and uterine colon cancer (HeLa) cells. The substantial cellular uptake of poly(thioether-ester) nanoparticles by HeLa cells suggests a potential use in uterine colon cancer treatment.

Cellulase immobilization on magnetic nanoparticles encapsulated in polymer nanospheres.

Immobilization of cellulases on magnetic nanoparticles, especially magnetite nanoparticles, has been the main approach studied to make this enzyme, economically and industrially, more attractive. However, magnetite nanoparticles tend to agglomerate, are very reactive and easily oxidized in air, which has strong impact on their useful life. Thus, it is very important to provide proper surface coating to avoid the mentioned problems. This study aimed to investigate the immobilization of cellulase on magnetic nanoparticles encapsulated in polymeric nanospheres. The support was characterized in terms of morphology, average diameter, magnetic behavior and thermal decomposition analyses. The polymer nanospheres containing encapsulated magnetic nanoparticles showed superparamagnetic behavior and intensity average diameter about 150 nm. Immobilized cellulase exhibited broader temperature stability than in the free form and great reusability capacity, 69% of the initial enzyme activity was maintained after eight cycles of use. The magnetic support showed potential for cellulase immobilization and allowed fast and easy biocatalyst recovery through a single magnet.

Increased cellular uptake of lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles due to surface modification with folic acid.

Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid were synthesized by miniemulsion polymerization in just one step. In vitro biocompatibility and cytotoxicity assays on L929 (murine fibroblast), human red blood, and HeLa (uterine colon cancer) cells were performed. The effect of folic acid at the nanoparticles surface was evaluated through cellular uptake assays in HeLa cells. Results showed that the presence of folic acid did not affect substantially the polymer particle size (~120 nm), the superparamagnetic behavior, the encapsulation efficiency of lauryl gallate (~87 %), the Zeta potential (~38 mV) of the polymeric nanoparticles or the release profile of lauryl gallate. The release profile of lauryl gallate from superparamagnetic poly(methyl methacrylate) nanoparticles presented an initial burst effect (0-1 h) followed by a slow and sustained release, indicating a biphasic release system. Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles with folic acid did not present cytotoxicity effects on L929 and human red blood cells. However, free lauryl gallate presented significant cytotoxic effects on L929 and human red blood cells at all tested concentrations. The presence of folic acid increased the cytotoxicity of lauryl gallate loaded in nanoparticles on HeLa cells due to a higher cellular uptake when HeLa cells were incubated at 37 °C. On the other hand, when the nanoparticles were incubated at low temperature (4 °C) cellular uptake was not observed, suggesting that the uptake occurred by folate receptor mediated energy-dependent endocytosis. Based on presented results our work suggests that this carrier system can be an excellent alternative in targeted drug delivery by folate receptor.

Immobilization of Candida antarctica Lipase B on Magnetic Poly(Urea-Urethane) Nanoparticles.

Poly(urea-urethane) (PUU) nanoparticles with encapsulated superparamagnetic magnetite (Fe3O4) were obtained by interfacial miniemulsion polymerization and used as support for immobilization of lipase B from Candida antarctica (CALB). CALB enzyme was immobilized on magnetic PUU nanoparticles in two steps. The enzyme was immobilized in the lyophilized nanoparticles (magnetic PUU) after the support synthesis in phosphate buffer (pH 7.6) containing CALB, by the contact between nanoparticles and enzymatic solution. The mixture was incubated at 30 °C in an orbital shaker during 0.5 until 6 h to determine the time for maximum immobilization efficiency. The enzyme activity was determined by esterification reactions between lauric acid and propanol. Residual activities above 95 % in relation to free enzyme were obtained in 1 h of immobilization with enzyme concentration of 0.55 mg/mL. FTIR spectrum and SEM-FEG images were used to confirm the presence of CALB on magnetic support after immobilization and stability of support even after immobilization process, respectively. Thermal (40, 60, and 80 °C) and pH (pH 4, 7, and 10) stabilities, storage stability, and reuse were evaluated. CALB immobilized derivatives showed high stabilities with residual activities of 95, 100, and 100 % at 40, 60, and 80 °C, respectively, in 6 h of incubation. After incubation in different pH values, CALB immobilized derivative presented activities of 81, 76, and 69 % in relation to activities in the beginning of the stabilization process in pH 4, 7, and 10, respectively. Furthermore, CALB immobilized derivative reduces only 15 % of its activity after 30 days of storage at 4 °C. Reuse results showed that immobilized CALB on magnetic PUU nanoparticles led to 95 % of geranyl oleate conversion after 8 cycles of application demonstrating high stability of the CALB immobilized derivative under different conditions.

Synthesis of PEG-PCL-based polyurethane nanoparticles by miniemulsion polymerization.

In this work biocompatible polyurethane nanoparticles for future application as noninvasive polymeric nanocarriers using propellant-based inhalers in the treatment of respiratory diseases were prepared by miniemulsion interfacial polymerization derived from isophorone diisocyanate, poly(ϵ-caprolactone), and poly(ethylene glycol). The effects of the surfactant type, nonionic Tween 80 and Brij 35, anionic sodium dodecyl sulfate, and cationic cetyltrimethyl ammonium bromide, and poly(ethylene glycol) molar mass on the stability, size and morphology of nanoparticles were evaluated. In addition, the ability of cells to proliferate in contact with polyurethane nanoparticles was assessed by MTS ([(3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium, inner salt]) assay using human lung adenocarcinoma A549 cells, an in vitro model of Type II alveolar epithelium.

Infection related to implantable central venous access devices in cancer patients: epidemiology and risk factors.

OBJECTIVE: To describe the epidemiology of infections related to the use of implantable central venous access devices (CVADs) in cancer patients and to evaluate measures aimed at reducing the rates of such infections. DESIGN: Prospective cohort study. SETTING: Referral hospital for cancer in São Paulo, Brazil. PATIENTS: We prospectively evaluated all implantable CVADs employed between January 2009 and December 2011. Inpatients and outpatients were followed until catheter removal, transfer to another facility, or death. METHODS: Outcome measures were bloodstream infection and pocket infection. We also evaluated the effects that the creation of a multidisciplinary team for CVAD care, avoiding in-hospital implantation of CVADs, and limiting CVAD insertion in neutropenic patients have on the rates of such infections. RESULTS: During the study period, 966 CVADs (mostly venous ports) were implanted in 933 patients, for a combined total of 243,792 catheter-days. We identified 184 episodes of infection: 154 (84%) were bloodstream infections, 21 (11%) were pocket infections, and 9 (5%) were surgical site infections. During the study period, the rate of CVAD-related infection dropped from 2.2 to 0.24 per 1,000 catheter-days ([Formula: see text]). Multivariate analysis revealed that relevant risk factors for such infection include surgical reintervention, implantation in a neutropenic patient, in-hospital implantation, use of a cuffed catheter, and nonchemotherapy indication for catheter use. CONCLUSIONS: Establishing a multidisciplinary team specifically focused on CVAD care, together with systematic reporting of infections, appears to reduce the rates of infection related to the use of these devices.