Quantitative analysis of pore patterns on rat prostate nuclei using spatial statistics methods

Spatial statistics methods have been used to analyse the nuclear pore pattern in rat ventral prostate nuclei isolated from adult animals. The observed results show that: (1) pores on prostate nuclear membranes are not randomly distributed; (2) the data sets obtained from different micrographs are consistent with the same statistical model thus suggesting the existence of a typical pore distribution.     

Design of polymeric nanoparticles and its applications as drug delivery systems for acne treatment

Objective: The aim of this study was to evaluate a formulation made of poly(lactide-co-glycolide) (PLGA) nanoparticles containing azelaic acid for potential acne treatment.

Methods: Azelaic acid-loaded PLGA nanoparticles were prepared by spontaneous emulsification processes using poloxamer 188 as stabilizer. Several manufacturing parameters such as stirring rate, concentration of stabilizer and different recovery methods were investigated. Nanoparticles were evaluated in terms of size, zeta potential, encapsulation efficiency, release kinetics and permeation kinetics in vitro. Furthermore, in vitro toxicological studies were performed in Saccharomyces cerevisiae model.

Results: The results showed that by adjusting some formulation conditions it was possible to obtain nanoparticles with high loading and a controlled drug release. Freeze-dried recovery altered the nanoparticles structure by enhancing porous structures and mannitol was required to control the mean particle size. The centrifugation recovery was found to be the best approach to nanoparticles recovery. Similar toxicity profiles were observed for both drug-free and azelaic acid-loaded nanoparticles, with concentration-dependent decreases in cell viability.

Conclusion: These results indicate a potential formulation for controlled release delivery of azelaic acid to the follicular unit.     

Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil,and Doxorubicin Using In Silico Approaches

Chemotherapy is the main treatment for most early-stage cancers; nevertheless, its efficacy is usually limited by drug resistance, toxicity, and tumor heterogeneity. Cell-penetrating peptides (CPPs) are small peptide sequences that can be used to increase the delivery rate of chemotherapeutic drugs to the tumor site, therefore contributing to overcoming these problems and enhancing the efficacy of chemotherapy. The drug combination is another promising strategy to overcome the aforementioned problems since the combined drugs can synergize through interconnected biological processes and target different pathways simultaneously. Here, we hypothesized that different peptides (P1–P4) could be used to enhance the delivery of chemotherapeutic agents into three different cancer cells (HT-29, MCF-7, and PC-3). In silico studies were performed to simulate the pharmacokinetic (PK) parameters of each peptide and antineoplastic agent to help predict synergistic interactions in vitro. These simulations predicted peptides P2–P4 to have higher bioavailability and lower T_max, as well as the chemotherapeutic agent 5-fluorouracil (5-FU) to have enhanced permeability properties over other antineoplastic agents, with P3 having prominent accumulation in the colon. In vitro studies were then performed to evaluate the combination of each peptide with the chemotherapeutic agents as well as to assess the nature of drug interactions through the quantification of the Combination Index (CI). Our findings in MCF-7 and PC-3 cancer cells demonstrated that the combination of these peptides with paclitaxel (PTX) and doxorubicin (DOXO), respectively, is not advantageous over a single treatment with the chemotherapeutic agent. In the case of HT-29 colorectal cancer cells, the combination of P2–P4 with 5-FU resulted in synergistic cytotoxic effects, as predicted by the in silico simulations. Taken together, these findings demonstrate that these CPP6-conjugates can be used as adjuvant agents to increase the delivery of 5-FU into HT-29 colorectal cancer cells. Moreover, these results support the use of in silico approaches for the prediction of the interaction between drugs in combination therapy for cancer.     

Creative discovery in the lexical “validation gap”

Compound terms play a surprisingly key role in the organization of lexical ontologies. However, their inclusion forces one to address the issues of completeness and consistency that naturally arise from this organizational role. In this paper, we show how creative exploration in the space of literal compounds can reveal not only additional compound terms to systematically balance an ontology, but can also discover new and potentially innovative concepts in their own right.     

A new control strategy for an AC/DC converter based on a piezoelectric transformer

Piezoelectric transformers (PTs) are an attractive solution to reduce size and weight in ac/dc converters. In this paper, a PT-based topology is presented together with a control method. As an application, an 8-W ac/dc adapter (110 V/sub AC/ input, 12 V/sub DC/ output) is presented operating at frequencies around 500 kHz.     

Intercontinental spread of a multidrug-resistant methicillin-resistant Staphylococcus aureus clone

Two hundred ten methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered between 1990 and 1997 from three Portuguese hospitals located in Lisbon and Oporto were analyzed by molecular fingerprinting techniques. The hybridization of ClaI restriction digests with the mecA- and Tn554-specific DNA probes combined with pulsed-field gel electrophoresis documented the abrupt appearance and extensive intrahospital spread of the Brazilian epidemic MRSA clone in the 1995 samples of each one of the three hospitals analyzed-suggesting the intercontinental transfer of this strain from Brazil to Portugal. The appearance of this clone may challenge the dominance of another highly epidemic imported clone-the Iberian MRSA, currently the most widely spread MRSA clone in Portuguese hospitals.     

Transposition of the EU cogeneration directive: A vision for Portugal

The potential for new, small-scale and micro-cogeneration installations in Portugal is very considerable due to the number of potential host buildings. In this work, we discuss the legal framework of the Portuguese energy market, and some modifications to accommodate the Directive, 2004/8/EC are stressed. A practical case of cogeneration is also presented, showing the application of the Annex III (b) and (c) of the Cogeneration Directive. The practical case presented shows that micro CHP can be considered highly efficient, with parameters calculated with the Directive rules. Two main improvements in Portugal's energy policy are important: improvement on the permission to access grid system and improvement on support mechanisms indexing it to PES. The Cogeneration Directive transposition is an excellent opportunity to induce a less restrictive framework for the installation of new cogeneration systems, reducing the technological barriers, namely allowing medium-voltage connection with the grid, and improving the revenues provided from these small cogeneration systems. These modifications can improve significantly the number of potential hosts for small-scale cogeneration systems.     

A scheme to analyze conducting plates of resonant size using theconjugate-gradient method and the fast Fourier transform

A scheme for analyzing electrodynamic problems involving conducting plates of resonant size using the conjugate-gradient (CG) method and the fast Fourier transform (FFT) is presented in detail. The problems are analyzed by solving their corresponding electric-field integral equation. The procedure is made easy and systematic by using a sampling process with rooftop functions to represent the induced current and pulses to average the fields. These functions have been widely used in moment-method (MM) applications. The scheme is an efficient numerical tool, benefiting from the good convergence and low memory requirements of the CG and the low CPU time consumed in performing convolutions with the FFT. In comparison with the MM, the scheme avoids the storage of large matrices and reduces the computer time by an order of magnitude. Several results are presented and compared with analytical, numerical, or measured values that appear in the literature     

Absorption of anthocyanins through intestinal epithelial cells – Putative involvement of GLUT2

Anthocyanins bioavailability is a major issue regarding their biological effects and remains unclear due to few data available on this matter. This work aimed to evaluate the absorption of anthocyanins at the intestine using Caco‐2 cells. Anthocyanin extract, rich in malvidin‐3‐glucoside, was obtained from red grape skins and tested on Caco‐2 cells. The absorption of anthocyanins, in absence or presence of 1% ethanol, was detected by HPLC/DAD/LC‐MS. Our results showed that this transport was significantly increased in the presence of ethanol especially after 60 min of incubation. In addition, cells that were pretreated for 96 h with anthocyanins (200 μg/mL) showed an increase of their own transport (about 50% increase). Expression of glucose transporters sodium‐dependent glucose transporter 1, facilitative glucose transporters 5, and facilitative glucose transporters 2 was assessed by RT‐PCR. It was found that facilitative glucose transporters 2 expression was increased (60%) in Caco‐2 cells pretreated with anthocyanins, by comparison with controls. When the effect of anthocyanin extract on ³H‐2‐deoxy‐D ‐glucose uptake was tested, an inhibitory effect was observed (about 60% decrease). However, the malvidin aglycone was tested and had no effect. In conclusion, anthocyanins could be absorbed through Caco‐2 cells, and can interfere with their own transport and also with glucose intestinal uptake.