Successful therapies for Alzheimer's disease: why so many in animal models and none in humans?

Peering into the field of Alzheimer's disease (AD), the outsider realizes that many of the therapeutic strategies tested (in animal models) have been successful. One also may notice that there is a deficit in translational research, i.e., to take a successful drug in mice and translate it to the patient. Efforts are still focused on novel projects to expand the therapeutic arsenal to 'cure mice.' Scientific reasons behind so many successful strategies are not obvious. This article aims to review the current approaches to combat AD and to open a debate on common mechanisms of cognitive enhancement and neuroprotection. In short, either the rodent models are not good and should be discontinued, or we should extract the most useful information from those models. An example of a question that may be debated for the advancement in AD therapy is: In addition to reducing amyloid and tau pathologies, would it be necessary to boost synaptic strength and cognition? The debate could provide clues to turn around the current negative output in generating effective drugs for patients. Furthermore, discovery of biomarkers in human body fluids, and a clear distinction between cognitive enhancers and disease modifying strategies, should be instrumental for advancing in anti-AD drug discovery.

Imobilização de enzimas a partir de "kit" comercial: determinação de parâmetros metabólicos em sangue animal empregando multicomutação em fluxo

Automatic flow procedures based on the multicommutation concept, dedicated to the determination of 3-hydroxybutyrate, glucose and cholesterol are proposed. The enzymes were immobilized on glass beads and packed into mini-columns that were coupled to a flow system. Sampling throughputs of 55, 40 and 40 determinations per hour, linear response from 10 to 150, 50 to 600, 25 to 125 mg L-1, detection limits of 1.5, 14 and 4 mg L-1 and relative standard deviations of 1, 2 and 2% for 3-hydroxybutyrate, glucose and cholesterol, respectively, were achieved.

A Micromechanics-Based Damage Model for [± θ / 90n ]s Composite Laminates

A new damage model based on a micromechanical analysis of cracked [± θ / 90n ]s laminates subjected to multiaxial loads is proposed. The model predicts the onset and accumulation of transverse matrix cracks in uniformly stressed laminates, the effect of matrix cracks on the stiffness of the laminate, as well as the ultimate failure of the laminate. The model also accounts for the effect of the ply thickness on the ply strength. Predictions relating the elastic properties of several laminates and multiaxial loads are presented

A Thermodynamically Consistent Damage Model for Advanced Composites

A continuum damage model for the prediction of damage onset and structural collapse of structures manufactured in fiber-reinforced plastic laminates is proposed. The principal damage mechanisms occurring in the longitudinal and transverse directions of a ply are represented by a damage tensor that is fixed in space. Crack closure under load reversal effects are taken into account using damage variables established as a function of the sign of the components of the stress tensor. Damage activation functions based on the LaRC04 failure criteria are used to predict the different damage mechanisms occurring at the ply level. The constitutive damage model is implemented in a finite element code. The objectivity of the numerical model is assured by regularizing the dissipated energy at a material point using Bazant’s Crack Band Model. To verify the accuracy of the approach, analyses ofcoupon specimens were performed, and the numerical predictions were compared with experimental data

An Interface Damage Model for the Simulation of Delamination Under Variable-Mode Ratio in Composite Materials

A thermodynamically consistent damage model for the simulation of progressive delamination under variable mode ratio is presented. The model is formulated in the context of the Damage Mechanics. The constitutive equation that results from the definition of the free energy as a function of a damage variable is used to model the initiation and propagation of delamination. A new delamination initiation criterion is developed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. The formulation proposed accounts for crack closure effets avoiding interfacial penetration of two adjacent layers aftercomplete decohesion. The model is implemented in a finite element formulation. The numerical predictions given by the model are compared with experimental results

Animal sound : què se sent quan s’és una cabra?

Aquest projecte treballa sobre la possibilitat d'aplicar tècniques d'enregistrament binaural en animals, en concret, en una cabra domèstica. Mitjançant uns micròfons col·locats dins les seves orelles i una petita càmera de vídeo muntada sobre el seu cap, s'obté un material audiovisual que permet fer-se una idea aproximada de com és la seva percepció del món. En base a un estudi de cognició comparada, es pretén trobar maneres de transformar els enregistraments obtinguts per tal d'adaptar el marc psicoacústic humà al de l'animal. L'objectiu és que una persona pugui sentir com ho fa un animal, encara que sigui d'una manera aproximada. Els materials obtinguts al llarg dels enregistraments són el punt de partida per a la construcció de paisatges sonors i peces audiovisuals diverses. Així doncs, el treball s'inicia amb el disseny i construcció d'un micròfon binaural, continua amb enregistraments de camp en animals i acaba amb l'edició, el processat i la composició dels paisatges sonors finals.

Métodos de extração e qualidade da fração lipídica de matérias-primas de origem vegetal e animal

Methodologies of extraction of lipids from chicken breast and oats flakes were evaluated: Soxhlet, Folch et al., Bligh & Dyer and Hara & Radin. For chicken breast, the methods Soxhlet, Folch et al. and Bligh & Dyer presented the highest yields in total lipids. With oat flakes, the methods Soxhlet and Bligh & Dyer presented higher yields than the Hara & Radin and Folch et al. The Soxhlet method affected the quality of the lipid fraction in both samples. Extracted lipid components were separated by thin layer chromatography, the chloroform-methanol based was more efficient to extract the neutral and polar lipids.

Plasmid DNA damage induced by singlet molecular oxygen released from the naphthalene endoperoxide DHPNO2 and photoactivated methylene blue

To investigate oxidative lesions and strand breaks induction by singlet molecular oxygen (¹O2), supercoiled-DNA plasmid was treated with thermo-dissociated DHPNO2 and photoactivated-methylene blue. DNA lesions were detected by Fpg that cleaves DNA at certain oxidized bases, and T4-endoV, which cleaves DNA at cyclobutane pyrimidine dimers and apurinic/apyrimidinic (AP) sites. These cleavages form open relaxed-DNA structures, which are discriminated from supercoiled-DNA. DHPNO2 or photoactivated-MB treatments result in similar plasmid damage profile: low number of single-strand breaks or AP-sites and high frequency of Fpg-sensitive sites; confirming that base oxidation is the main product for both reactions and that ¹O2 might be the most likely intermediate that reacts with DNA.

Aspectos analíticos e regulatórios na determinação de resíduos de macrolídeos em alimentos de origem animal por cromatografia líquida associada à espectrometria de massas

This is an overview of LC-MS techniques applied for macrolide determination in food, including sample preparation and method validation, as well as the policies adopted by international agencies regarding their presence in food. Techniques for the analysis of macrolides in food normally include solid phase or liquid-liquid extraction followed by HPLC. UHPLC presents advantages in running time, detectability and solvent consumption. Triple-quadrupoles are the most common analyzers in instruments used for the determination of contaminants in food, but time-of-flight and ion-trap spectrometers have been successfully applied for analyses focusing on the investigation of structural formula or the presence of degradation products.

O estado da arte na determinação de resíduos de medicamentos veterinários em alimentos de origem animal empregando técnicas cromatográficas acopladas à espectrometria de massas

The determination of veterinary drug residues in foods of animal origin is an important issue because of the risk these compounds pose to human health in addition to their persistence and tendency to bioaccumulate. In recent years, significant progress has been made in the area and this review presents the state of the art in sample preparation procedures associated with chromatographic techniques coupled to mass spectrometry for multiresidue determination of veterinary drugs in food of animal origin at concentration levels suitable for the control of residues and contaminants in food.