Progress in animal experimentation ethics. A case study from a brazilian medical school and from the international medical literature

PURPOSE: This study describes in Brazil and in the global biomedical community the time course of the development of animal research welfare guidelines. METHODS: The database of the Ethics Committee of the Faculty of Medicine of Ribeirao Preto (EC/FMRP-USP), Brazil, was surveyed since its inception in 2002 as the regulations became more stringent to provide better protection of animal research welfare at this institution. Medline database was evaluated to identify the number of publications in the period between 1968 and 2008 that used research animals and were in compliance with established ethics guidelines. RESULTS: The EC/FMRP-USP evaluated 979 projects up until 2009. Most of the applications came from Department of Physiology and the most frequently requested species was the rat. In 2004, national research funding agencies started to request prior approval from institutional review ethics committees prior to application review and this requirement became federal law in Brazil in 2008. The analysis of international publications revealed a relative reduction in studies involving research animals (18% in 1968 to 7.5% in 2008). CONCLUSIONS: The present work showed that in the last four decades major changes occurred in the guidelines dictating use of research animals occurred and they are being adopted by developing countries. Moreover, animal welfare concern in the scientific community preceded the introduction of journal guidelines for this purpose. Furthermore, in Brazil it was anticipated that laws were needed to protect animal research welfare from being not upheld.

Metacontingencies, Experimentation and Nonhumans: Searching for Conceptual and Methodological Advances

Metacontingency has been described as the functional relation between interlocking behavioral contingencies, plus their direct and immediate effect, called aggregated product, and a selecting event dependent of such effect, called cultural consequence. The metacontingencies analysis enables the discussion of human behavior complexity in social systems. In the present study, we aimed to review and discuss: (a) the importance of basic behavioral processes analysis for the comprehension of social human phenomena; (b) the necessity of constructing and improving metacontingencies experimental models; (c) the current state of metacontingencies experimental investigations in humans; (d) the use of animal models as a way to control the effects of verbal behavior, among other variables, over cultural selection; (e) a concrete and illustrative proposal of an animal model of metacontingencies.

Progress in animal experimentation ethics: a case study from a Brazilian medical school and from the international medical literature

PURPOSE: This study describes in Brazil and in the global biomedical community the time course of the development of animal research welfare guidelines. METHODS: The database of the Ethics Committee of the Faculty of Medicine of Ribeirao Preto (EC/FMRP-USP), Brazil, was surveyed since its inception in 2002 as the regulations became more stringent to provide better protection of animal research welfare at this institution. Medline database was evaluated to identify the number of publications in the period between 1968 and 2008 that used research animals and were in compliance with established ethics guidelines. RESULTS: The EC/FMRP-USP evaluated 979 projects up until 2009. Most of the applications came from Department of Physiology and the most frequently requested species was the rat. In 2004, national research funding agencies started to request prior approval from institutional review ethics committees prior to application review and this requirement became federal law in Brazil in 2008. The analysis of international publications revealed a relative reduction in studies involving research animals (18% in 1968 to 7.5% in 2008). CONCLUSIONS: The present work showed that in the last four decades major changes occurred in the guidelines dictating use of research animals occurred and they are being adopted by developing countries. Moreover, animal welfare concern in the scientific community preceded the introduction of journal guidelines for this purpose. Furthermore, in Brazil it was anticipated that laws were needed to protect animal research welfare from being not upheld.

AcMus: an Open, Integrated Platform for Room Acoustics Research

This article describes the design, implementation, and experiences with AcMus, an open and integrated software platform for room acoustics research, which comprises tools for measurement, analysis, and simulation of rooms for music listening and production. Through use of affordable hardware, such as laptops, consumer audio interfaces and microphones, the software allows evaluation of relevant acoustical parameters with stable and consistent results, thus providing valuable information in the diagnosis of acoustical problems, as well as the possibility of simulating modifications in the room through analytical models. The system is open-source and based on a flexible and extensible Java plug-in framework, allowing for cross-platform portability, accessibility and experimentation, thus fostering collaboration of users, developers and researchers in the field of room acoustics.

Does Lithium Prevent Alzheimer's Disease?

Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.

Chemistry and Chemical Education Through Text and Image: Analysis of Twentieth Century Textbooks Used in Brazilian Context

Assuming that textbooks give literary expression to cultural and ideological values of a nation or group, we propose the analysis of chemistry textbooks used in Brazilian universities throughout the twentieth century. We analyzed iconographic and textual aspects of 31 textbooks which had significant diffusion in the context of Brazilian universities at that period. As a result of the iconographic analysis, nine categories of images were proposed: (1) laboratory and experimentation, (2) industry and production, (3) graphs and diagrams, (4) illustrations related to daily life, (5) models, (6) illustrations related to the history of science, (7) pictures or diagrams of animal, vegetable or mineral samples, (8) analogies and (9) concepts of physics. The distribution of images among the categories showed a different emphasis in the presentation of chemical content due to a commitment to different conceptions of chemistry over the period. So, we started with chemistry as an experimental science in the early twentieth century, with an emphasis change to the principles of chemistry from the 1950s, culminating in a chemistry of undeniable technological influence. Results showed that reflections not only on the history of science, but on the history of science education, may be useful for the improvement of science education.

When size makes a difference: allometry, life-history and morphological evolution of capuchins (Cebus) and squirrels (Saimiri) monkeys (Cebinae, Platyrrhini)

Abstract Background How are morphological evolution and developmental changes related? This rather old and intriguing question had a substantial boost after the 70s within the framework of heterochrony (changes in rates or timing of development) and nowadays has the potential to make another major leap forward through the combination of approaches: molecular biology, developmental experimentation, comparative systematic studies, geometric morphometrics and quantitative genetics. Here I take an integrated approach combining life-history comparative analyses, classical and geometric morphometrics applied to ontogenetic series to understand changes in size and shape which happen during the evolution of two New World Monkeys (NWM) sister genera. Results Cebus and Saimiri share the same basic allometric patterns in skull traits, a result robust to sexual and ontogenetic variation. If adults of both genera are compared in the same scale (discounting size differences) most differences are small and not statistically significant. These results are consistent using both approaches, classical and geometric Morphometrics. Cebus is a genus characterized by a number of peramorphic traits (adult-like) while Saimiri is a genus with paedomorphic (child like) traits. Yet, the whole clade Cebinae is characterized by a unique combination of very high pre-natal growth rates and relatively slow post-natal growth rates when compared to the rest of the NWM. Morphologically Cebinae can be considered paedomorphic in relation to the other NWM. Geometric morphometrics allows the precise separation of absolute size, shape variation associated with size (allometry), and shape variation non-associated with size. Interestingly, and despite the fact that they were extracted as independent factors (principal components), evolutionary allometry (those differences in allometric shape associated with intergeneric differences) and ontogenetic allometry (differences in allometric shape associated with ontogenetic variation within genus) are correlated within these two genera. Furthermore, morphological differences produced along these two axes are quite similar. Cebus and Saimiri are aligned along the same evolutionary allometry and have parallel ontogenetic allometry trajectories. Conclusion The evolution of these two Platyrrhini monkeys is basically due to a size differentiation (and consequently to shape changes associated with size). Many life-history changes are correlated or may be the causal agents in such evolution, such as delayed on-set of reproduction in Cebus and larger neonates in Saimiri.

The antioxidant response of the liver of male Swiss mice raised on a AIN 93 or commercial diet

Background: Reactive oxygen species (ROS) are formed under natural physiological conditions and are thought to play an important role in many human diseases. A wide range of antioxidants are involved in cellular defense mechanisms against ROS, which can be generated in excess during stressful conditions, these include enzymes and non-enzymatic antioxidants. The aim of this study was to evaluate the antioxidant responses of mice to two diets control, commercial and the purified AIN 93 diet, commonly used in experiments with rodents. Results: Malondialdehyde (MDA) and hydrogen peroxide (H2O2) concentrations and superoxide dismutase (SOD) and glutathione reductase (GR) activities determined in the liver were lower in the group of mice fed with the AIN 93 diet, while catalase (CAT) activity was higher in the same group, when compared to the group fed on the commercial diet. Liver glutathione peroxidase (GSH-Px) activity was similar in the groups fed on either AIN 93 or the commercial diets. Two SOD isoforms, Mn-SODII and a Cu/Zn-SODV, were specifically reduced in the liver of the AIN 93 diet fed animals. Conclusions: The clear differences in antioxidant responses observed in the livers of mice fed on the two diets suggest that the macro- and micro-nutrient components with antioxidant properties, including vitamin E, can promote changes in the activity of enzymes involved in the removal of the ROS generated by cell metabolism.

A sepse como causa de lesão renal aguda: modelo experimental

A sepse associada à falência de múltiplos órgãos como a lesão renal aguda (LRA) demonstra alta taxa de mortalidade no paciente crítico. Este estudo investigou a LRA induzida pela sepse em modelo experimental. Foram utilizados ratos da raça Wistar, adultos e machos divididos nos seguintes grupos: Controle - controle cirúrgico e Sepse - indução da sepse pela ligadura e punção do cécon (LPC). Foram avaliados os parâmetros fisiológicos (temperatura retal, pressão arterial média - PAM, glicemia sérica e fluxo urinário); a função renal (clearance de creatinina); o estresse oxidativo (peróxidos urinários e substâncias reativas com ácido tiobarbitúrico - TBARS) e realizada a análise histológica renal. O estudo conclui que a LRA induzida pela sepse caracteriza-se por lesão endotelial com disfunção hemodinâmica, liberação de mediadores inflamatórios e geração de espécies reativas de oxigênio (EROs) por células tubulares, caracterizando-se como uma associação de vasoconstrição renal de origem hemodinâmica e inflamatória.

Estudo in vivo do comportamento de bioprótese liofilizada: seguimento de 3 meses em carneiros jovens

OBJETIVO: Para melhorar as propriedades mecânicas e imunogênicas, o glutaraldeído é utilizado no tratamento do pericárdio bovino que é utilizado em biopróteses. A liofilização do pericárdio bovino tratado com glutaraldeído diminui os radicais aldeído, com provável redução do potencial para calcificação. O objetivo deste estudo é avaliar os efeitos da liofilização em biopróteses valvares de pericárdio bovino como mecanismo protetor na diminuição da disfunção estrutural valvar. MÉTODOS: Foi realizado o implante de biopróteses de pericárdio bovino tratado com glutaraldeído, liofilizadas ou não, em carneiros de 6 meses de idade, sendo os animais eutanasiados com 3 meses de seguimento. As biopróteses foram implantadas em posição pulmonar, com auxílio de circulação extracorpórea. Um grupo controle e outro grupo liofilizado foram avaliados quanto ao gradiente ventrículo direito/artéria pulmonar (VD/AP) no implante e explante; análise quantitativa de cálcio; inflamação; trombose e pannus. O nível de significância estabelecido foi de 5%. RESULTADOS: O gradiente médio VD/AP, no grupo controle, no implante, foi 2,04 ± 1,56 mmHg e, no grupo de liofilização, foi 6,61 ± 4,03 mmHg. No explante, esse gradiente aumentou para 7,71 ± 3,92 mmHg e 8,24 ± 6,2 mmHg, respectivamente, nos grupos controle e liofilização. O teor de cálcio médio, após 3 meses, nas biopróteses do grupo controle foi 21,6 ± 39,12 µg Ca+2/mg de peso seco, em comparação com um teor médio de 41,19 ± 46,85 µg Ca+2/mg de peso seco no grupo liofilizado (P = 0,662). CONCLUSÃO: A liofilização de próteses valvares com pericárdio bovino tratado com glutaraldeído não demonstrou diminuição da calcificação neste experimento.