The enduring scientific contributions of Sigmund Freud

Through the development of a novel observational method, Sigmund Freud made possible the collection of reliable data about man's inner life. The scientific hypotheses he formulated about these formed the initial version of psychoanalysis. Many of these first thoughts have had to be revised in the light of subsequent scientific findings about the operations of the central nervous system, but even these refuted propositions often had much heuristic value. Despite the passage of a whole century, many Freudian hypotheses have retained their scientific standing. Most important among these was Freud's realization that human thought is usually unconscious. His understanding of the role of the automatic repetition of basic patterns of behavior, of the fateful consequences of early childhood emotional vicissitudes in structuring enduring mental dispositions, and of the distinction between two distinct modes of thinking are the most significant among his many contributions.     

The implications of microarray technology for animal use in scientific research

Microarray technology has the potential to affect the number of laboratory animals used, the severity of animal experiments, and the development of non-animal alternatives in several areas scientific research. Microarrays can contain hundreds or thousands of microscopic spots of DNA, immobilised on a solid support, and their use enables global patterns of gene expression to be determined in a single experiment. This technology is being used to improve our understanding of the operation of biological systems during health and disease, and their responses to chemical insults. Although it is impossible to predict with certainty any future trends regarding animal use, microarray technology might not initially reduce animal use, as is often claimed to be the case. The accelerated pace of research as a result of the use of microarrays could increase overall animal use in basic and applied biological research, by increasing the numbers of interesting genes identified for further analysis, and the number of potential targets for drug development. Each new lead will require further evaluation i n studies that could involve animals. In toxicity testing, microarray studies could lead to increases in animal studies, if further confirmatory and other studies are performed. However, before such technology can be used more extensively, several technical problems need to be overcome, and the relevance of the data to biological processes needs to be assessed. Were microarray technology to be used in the manner envisaged by its protagonists, there need to be efforts to increase the likelihood that its application will create new opportunities for reducing, refining and replacing animal use. This comment is a critical assessment of the possible implications of the application of microarray technology on animal experimentation in various research areas, and makes some recommendations for maximising the application of the Three Rs.     

The Brazilian legal framework on the scientific use of animals

Brazil has an exceptionally dynamic research sector in Latin America in health, biotechnology, and pharmacology, backed by defined government policies on science and technology and a health research agenda focusing on important neglected diseases: malaria, leishmaniasis, Chagas disease, turberculosis, leprosy, and dengue. The Brazilian health research policy promotes partnerships and networks among scientists in academic institutions in both wealthy industrialized and disease-endemic countries, and in these efforts the government's guidelines for animal use in biomedical research are considered fundamental to guarantee both animal welfare and the quality of research. Given international discussions of animal experimentation regulations and guidelines, in this article we describe current Brazilian legislation governing the use of animals in scientific investigations. We conclude that, despite advances in the implementation of the 3Rs (reduction, refinement, replacement), the new regulatory framework does not sufficiently incorporate ethical considerations, lacking explicit reference to the 3Rs as well as measures for their full application. The more humane use of animals in research will depend on the approach adopted by Brazil's National Council for the Control of Animal Experimentation to promote the 3Rs and to improve internal regulations as well as data collection and analysis in research institutions. In Brazil as elsewhere, one of the greatest challenges to policymakers is to harmonize the myriad and intertwined legal provisions without hindering biomedical research.     

The use of biotin-streptavidin systems for enhancing the parameters of immunometric analysis

The possibility of improving analytical parameters of the immunometric assay with the use of biotinylated antibodies and biotin-streptavidin complexes in comparison with the commonly known approach of direct antibody modification with 125I has been studied. Experiments have been carried out with the use of low-affinity antibodies (Kass approximately 10(9) M-1) to ferritin. The signal-to-noise ratio in the immunometric increases 2.3 times when streptavidin labeled with horse-radish peroxidase is used and 4.3 times when the preformed streptavidin + biotin-peroxidase complex is used in comparison with assay systems based on 125I-labeled antibodies. The improvement of assay parameters of immunochemical systems by means of biotin-streptavidin complexes has been found to permit the use of low-affinity antibodies as assay reagents, thus ensuring analytical parameters attaining or close to those of immunoradiometric assay systems based on high-affinity 125I-labeled antibodies (Kass approximately 10(10) M-1). As shown in this study, the following factors ensure the signal enhancement in biotin-streptoavidin systems: (a) the biotin modification of several lysin residues per IgG molecule, the optimum extent of modification being 3-4 residues per molecule; (b) mild procedure for biotinylation. In contrast to oxidative iodination, the modification of NH2 groups with biotin esters does not significantly affect their antigen-binding properties.     

The appropriate use of regression equations for the estimation of segmental inertia parameters

Linear regression equations are commonly used in conjunction with experimental data to provide linear relationships between quantities which are dimensionally distinct. In many cases theoretical relationships between such quantities are known and can be used as a basis for non-linear regression equations. This study compares linear and non-linear approaches for estimating the segmental moments of inertia from anthropometric measurements using the data of Chandler et al. [Chandler et al. (1975) Investigation of inertial properties of the human body. AMRL Technical Report 74-137, Wright Patterson Air Force Base. OH.] Right limb data were used to derive the equations while left limb data were used as a cross-validation sample to evaluate the inertia estimates calculated from the equations. For the limb segments the standard error estimates had average values of 21% for the linear equations and 13% for the non-linear equations. Data on a 10 yr-old boy was used to compare the two approaches outside the sample range. The mean percentage residuals were 286% for the linear equations and 20% for the non-linear equations. A set of non-linear equations is provided.     

The scientific evaluation of the thermal environment of cave dwellings in China

1. 1. The conclusion drawn from the result of the research work carried out is that the majority of the existing cave dwellings are not warm in winter and are cool in summer.

2. 2. Unless these cave dwellings are improved they are not suitable and pleasant places for people to live in.

3. 3. Therefore the following measures should be taken so as to improve the quality of the cave dwellings: (i) in summer more fresh air should be let in to replace the state air and the air should be dehumidified to solve the problem of being too cool and humid; and (ii) in winter the geothermal energy and the solar energy should be made full use of, in addition, there should be local heating in the cave dwellings.

The use of primary hepatocyte cultures for the evaluation of chemoprotective agents

Primary cultures of human and rat hepatocytes are widely used in pharmacotoxicological research. This model presents the advantages of retaining liver function for at least a few days, expressing both phase 1 and phase 2 enzymes, and responding to inducers. Recently we made use of primary hepatocytes to investigate the effects of chemoprotective agents on drug-metabolizing enzyme expression and activities. The treatment of rat and human hepatocytes with two chemoprotective agents, oltipraz (a synthetic derivative of 1,2-dithiole-3-thione) and sulforaphane (an isothiocyanate found in broccoli), clearly demonstrated that both of these compounds are inducers of glutathione transferases and transient inhibitors of cytochrome P450, suggesting that these two compounds could exert their chemoprotective effects by both reducing the formation of reactive metabolites of chemicals and enhancing their inactivation.     

The use of the spectrophotometric analysis for the calculation of the thermodynamic parameters in actinocin derivative-DNA systems

The spectral properties of the actinocin derivative ActII in complexes with DNA were studied by UV visible spectrophotometry. Two binding models with one and two binding sites for competitive binding with different values of parameters were considered. To choose an optimal model of complexation, the optimization program of spectrophotometric concentration dependencies DALSMOD was used. Using this program, it was concluded that at least three complexes with different absorption spectra are present in the system ActII-DNA. The logarithms of K2 and K3 for DNA-ActII mixtures, calculated for models I and II at different sodium ion concentrations, were in good agreement with predictions of the counterion condensation theory. The analysis of the absorption spectra of ActII-DNA mixtures at different temperatures made it possible to obtain the values of deltaH and deltaS for each type of complexes. The values of entropy deltaS were positive in the 0.02 M NaCl solution and negative in the 0.15 M NaCI solution.     

The use of environmental media evaluation guides for screening environmental contamination

In conducting health assessments at hazardous‐waste sites, ATSDR staff must identify environmental chemical contaminants that pose a potential public health hazard. To assist health assessors in this effort, ATSDR has developed environmental media evaluation guides (EMEGs). EMEGs have been developed for water, soil, and air. The EMEG values are expressed as a range to account for the range in exposures in different segments of the population. The use of EMEGs provides health assessors with a consistent strategy for selecting environmental contaminants to be further evaluated in the health assessment process.