Preparation and Properties of PTFE-PMMA Core-Shell Nanoparticles and Nanocomposites

he preparation of polytetrafluoroethylene-poly(methyl methacrylate) (PTFE-PMMA) core-shell particles was described, featuring controlled size and narrow size distribution over a wide compositional range, through a seeded emulsion polymerization starting from a PTFE seed of 26 nanometers. Over the entire MMA/PTFE range, the particle size increases as the MMA/PTFE ratio increases. A very precise control over the particle size can be exerted by properly adjusting the ratio between the monomer and the PTFE seed. Particles in the 80240 nm range can be prepared with uniformity indexes suited to build 2D and 3D colloidal crystals. These core-shell particles were employed to prepare nanocomposites with different compositions, through an annealing procedure at a temperature higher than the glass transition temperature of the shell forming polymer. A perfect dispersion of the PTFE particles within the PMMA matrix was obtained and optically transparent nanocomposites were prepared containing a very high PTFE amount

Biomarkers of sensitivity to potent and selective antitumor 2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F203) in ovarian cancer

2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F203, NSC 703786) lysylamide belongs to a novel mechanistic class of antitumor agents. It elicits activity against ovarian, breast, kidney and colorectal cancer models. In sensitive breast cancer cells, 5F203 activates aryl hydrocarbon receptor (AhR) signaling. Herein, we evaluate the role of AhR in 5F203 activity in two ovarian cancer cell lines: IGROV-1 (sensitive to 5F203), SKOV-3 (resistant to this agent). In addition, cancer cells have been isolated from ascites fluid of ovarian cancer patients; sensitivity to 5F203 and concurrent AhR signal transduction has been examined in ascites-isolated ovarian cancer patients' cells. 5F203 induced enhanced CYP1A1 expression, AhR translocation and ROS formation in IGROV-1 cells and ascites-isolated ovarian cancer cells that were sensitive to 5F203. In IGROV-1 cells 5F203-induced ROS formation was accompanied by JNK, ERK and P38MAPK phosphorylation, DNA damage and cell cycle arrest prior to apoptosis. In contrast, 5F203 failed to induce CYP1A1 expression, AhR translocation or oxidative stress in 5F203-resistant SKOV-3 cells, or in ovarian cancer ascites cells inherently resistant to this agent. We propose that AhR may represent a new molecular target in the treatment of ovarian tumors and 5F203 may exemplify a potential novel treatment. Furthermore, putative biomarkers of sensitivity to this agent have been identified.Fil: Callero, Mariana Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luzzani, Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Dios, Diana O.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Bradshaw, Tracey D.. The University Of Nottingham; Reino UnidoFil: Loaiza Perez, Andrea Irene. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases

This article analyzes the "Global Burden of Disease Study 2010" and examines the study's implications for neglected tropical diseases

A randomized clinical trial to determine the effectiveness of CO-oximetry and anti-smoking brief advice in a cohort of kidney transplant patients who smoke: study protocol for a randomized controlled trial

BACKGROUND: The cardiovascular risk in renal transplant patients is increased in patients who continue to smoke after transplantation. The aim of the study is to measure the effectiveness of exhaled carbon monoxide (CO) measurement plus brief advisory sessions, in comparison to brief advice, to reduce smoking exposure and smoking behavior in kidney transplant recipients who smoke. The effectiveness will be measured by: (1) abandonment of smoking, (2) increase in motivation to stop smoking, and (3) reduction in the number of cigarettes smoked per day. METHODS/DESIGN: Design: a randomized, controlled, open clinical trial with blinded evaluation. Scope: A Coruña Hospital (Spain), reference to renal transplantation in the period 2012–2015. Inclusion criteria: renal transplant patients who smoke in the precontemplation, contemplation or preparation stages according to the Prochaska and DiClemente’s Stages of Change model, and who give their consent to participate. Exclusion criteria: smokers attempting to stop smoking, patients with terminal illness or mental disability that prevents them from participating. Randomization: patients will be randomized to the control group (brief advisory session) or the intervention group (brief advisory session plus measuring exhaled CO). The sample target size is n = 112, with 56 patients in each group. Allowing for up to 10 % loss to follow-up, this would provide 80 % power to detect a 13 % difference in attempting to give up smoking outcomes at a two-tailed significance level of 5 %. Measurements: sociodemographic characteristics, cardiovascular risk factors, treatment, rejection episodes, infections, self-reported smoking habit, drug use, level of dependence (the Fagerström test), stage of change (Prochaska and DiClemente’s Stages of Change model), and motivation to giving up smoking (the Richmond test). Response: the effectiveness will be evaluated every 3, 6, 9 and 12 months as: pattern of tobacco use (self-reported tobacco use), smoking cessation rates, carbon monoxide (CO) levels in exhaled air measured by CO-oximetry, urinary cotinine tests, nicotine dependence (Fagerström test), motivational stages of change (Prochaska and DiClemente’s stages) and motivation to stop smoking (the Richmond test). Analysis: descriptive statistics and linear/logistic multiple regression models will be performed. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. Ethics: informed consent of the patients and Ethical Review Board was obtained (code 2011/061). DISCUSSION: Tobacco is a modifiable risk factor that increase the risk of morbidity and mortality in kidney transplant recipients. If effectiveness of CO-oximetry is confirmed to reduce tobacco exposure, we would have an intervention that is easy to use, low cost and with great implications about cardiovascular risk prevention in these patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16615772. EudraCT number: 2015-002009-12

Cellular pharmacology studies of anticancer agents: recommendations from the EORTC-PAMM group

An increasing number of manuscripts focus on the in vitro evaluation of established and novel anti-tumour agents in experimental models. Whilst the design of such in vitro assays is inherently flexible, some of these studies lack the minimum information necessary to critically evaluate their relevance or have been carried out under unsuitable conditions. The use of appropriate and robust methods and experimental design has important implications for generating results that are reliable, relevant, and reproducible. The Pharmacology and Molecular Mechanisms (PAMM) group of the European Organization for Research and Treatment of Cancer (EORTC) is the largest group of academic scientists working on drug development and bundle decades of expertise in this field. This position paper addresses all researchers with an interest in the preclinical and cellular pharmacology of anti-tumour agents and aims at generating basic recommendations for the correct use of compounds to be tested for anti-tumour activity using a range of preclinical cellular models of cancer

Decoding 2D-PAGE complex maps: Relevance to proteomics

This review describes two mathematical approaches useful for decoding the complex signal of 2D-PAGE maps of protein mixtures. These methods are helpful for interpreting the large amount of data of each 2D-PAGE map by extracting all the analytical information hidden therein by spot overlapping. Here the basic theory and application to 2D-PAGE maps are reviewed: the means for extracting information from the experimental data and their relevance to proteomics are discussed. One method is based on the quantitative theory of statistical model of peak overlapping (SMO) using the spot experimental data (intensity and spatial coordinates). The second method is based on the study of the 2D-autocovariance function (2D-ACVF) computed on the experimental digitised map. They are two independent methods that are able to extract equal and complementary information from the 2D-PAGE map. Both methods permit to obtain fundamental information on the sample complexity and the separation performance and to single out ordered patterns present in spot positions: the availability of two independent procedures to compute the same separation parameters is a powerful tool to estimate the reliability of the obtained results. The SMO procedure is an unique tool to quantitatively estimate the degree of spot overlapping present in the map, while the 2D-ACVF method is particularly powerful in simply singling out the presence of order in the spot position from the complexity of the whole 2D map, i.e., spot trains. The procedures were validated by extensive numerical computation on computer-generated maps describing experimental 2D-PAGE gels of protein mixtures. Their applicability to real samples was tested on reference maps obtained from literature sources. The review describes the most relevant information for proteomics: sample complexity, separation performance, overlapping extent, identification of spot trains related to post-translational modifications (PTMs)

Capillary electrophoresis of polymerase chain reaction-amplified products in polymer networks: the case of Kennedy's disease.

In Kennedy disease (an X-linked motoneuronal disorder associated with an increase in the number of (CAG)n triplet repeats in the first exon of the Androgen receptor gene; about twice as many as in normal conditions), polymerase chain reaction-amplified genic products exhibit two DNA fragments in the heterozygous female carriers, one with a range between 468 and 495 bp in the normal polymorphic population and a fragment corresponding to the pathological state that reaches 573 bp. These fragments are easily separated by gel-slab electrophoresis and detected by intercalating dye staining (ethidium bromide). As an alternative procedure, capillary zone electrophoresis in polymer networks, consisting of 8% polyacryloylaminoethoxyethanol at 0% cross-linker, offers a simple procedure for separation and on-line detection via UV absorbance at 254 nm, thus avoiding additional staining steps. The capillary column can be repeatedly used for up to 80-100 times and the electropherogram is stored on a magnetic support. Easy comparison among different runs is obtained by aligning all tracings to an internal standard of a 650 bp fragment added as a marker