Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex

Ropivacaine (RVC) is an enantiomerically pure local anesthetic (LA) largely used in surgical procedures, which presents physico-chemical and therapeutic properties similar to those of bupivacaine (BPV), but associated to less systemic toxicity This study focuses on the development and pharmacological evaluation of a RVC in 2-hydroxypropyl-beta-cyclodextrin (HP-P-CD) inclusion complex. Phase-solubility diagrams allowed the determination of the association constant between RVC and HP-beta-CD (9.46 M-1) and showed an increase on RVC solubility upon complexation. Release kinetics revealed a decrease on RVC release rate and reduced hemolytic effects after complexation. (onset at 3.7 mM and 11.2 mM for RVC and RVCHP-beta-CD, respectively) were observed. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray analysis (X-ray) showed the formation and the morphology of the complex. Nuclear magnetic resonance (NMR) and job-plot experiments afforded data regarding inclusion complex stoichiometry (1:1) and topology. Sciatic nerve blockade studies showed that RVCHP-beta-CD was able to reduce the latency without increasing the duration of motor blockade, but prolonging the duration and intensity of the sensory blockade (p < 0.001) induced by the LA in mice. These results identify the RVCHP-beta-CD complex as an effective novel approach to enhance the pharmacological effects of RVC, presenting it as a promising new anesthetic formulation. (c) 2007 Elsevier B.V All rights reserved.

Evaluation of the genotoxicity of cellulose nanofibers

Background: Agricultural products and by products provide the primary materials for a variety of technological applications in diverse industrial sectors. Agro-industrial wastes, such as cotton and curaua fibers, are used to prepare nanofibers for use in thermoplastic films, where they are combined with polymeric matrices, and in biomedical applications such as tissue engineering, amongst other applications. The development of products containing nanofibers offers a promising alternative for the use of agricultural products, adding value to the chains of production. However, the emergence of new nanotechnological products demands that their risks to human health and the environment be evaluated. This has resulted in the creation of the new area of nanotoxicology, which addresses the toxicological aspects of these materials.Purpose and methods: Contributing to these developments, the present work involved a genotoxicological study of different nanofibers, employing chromosomal aberration and comet assays, as well as cytogenetic and molecular analyses, to obtain preliminary information concerning nanofiber safety. The methodology consisted of exposure of Allium cepa roots, and animal cell cultures (lymphocytes and fibroblasts), to different types of nanofibers. Negative controls, without nanofibers present in the medium, were used for comparison.Results: The nanofibers induced different responses according to the cell type used. In plant cells, the most genotoxic nanofibers were those derived from green, white, and brown cotton, and curaua, while genotoxicity in animal cells was observed using nanofibers from brown cotton and curaua. An important finding was that ruby cotton nanofibers did not cause any significant DNA breaks in the cell types employed.Conclusion: This work demonstrates the feasibility of determining the genotoxic potential of nanofibers derived from plant cellulose to obtain information vital both for the future usage of these materials in agribusiness and for an understanding of their environmental impacts.

Application of fuzzy logic for the evaluation of livestock slaughtering

A lógica fuzzy admite infinitos valores lógicos intermediários entre o falso e o verdadeiro. Com esse princípio, foi elaborado neste trabalho um sistema baseado em regras fuzzy, que indicam o índice de massa corporal de animais ruminantes com objetivo de obter o melhor momento para o abate. O sistema fuzzy desenvolvido teve como entradas as variáveis massa e altura, e a saída um novo índice de massa corporal, denominado Índice de Massa Corporal Fuzzy (IMC Fuzzy), que poderá servir como um sistema de detecção do momento de abate de bovinos, comparando-os entre si através das variáveis linguísticas )Muito BaixaM, ,BaixaB, ,MédiaM, ,AltaA e Muito AltaM. Para a demonstração e aplicação da utilização deste sistema fuzzy, foi feita uma análise de 147 vacas da raça Nelore, determinando os valores do IMC Fuzzy para cada animal e indicando a situação de massa corpórea de todo o rebanho. A validação realizada do sistema foi baseado em uma análise estatística, utilizando o coeficiente de correlação de Pearson 0,923, representando alta correlação positiva e indicando que o método proposto está adequado. Desta forma, o presente método possibilita a avaliação do rebanho, comparando cada animal do rebanho com seus pares do grupo, fornecendo desta forma um método quantitativo de tomada de decisão para o pecuarista. Também é possível concluir que o presente trabalho estabeleceu um método computacional baseado na lógica fuzzy capaz de imitar parte do raciocínio humano e interpretar o índice de massa corporal de qualquer tipo de espécie bovina e em qualquer região do País.