Brasil adere à luta contra sacrifício de animais em pesquisas científicas

Animais em pesquisas

O Brasil finalmente vai ganhar um laboratório destinado a evitar o sacrifício de animais nas pesquisas científicas.

Os animais foram importantes durante uma longa fase da ciência e da medicina, mas hoje já existem várias técnicas que evitam o sacrifício a cada teste de uma molécula ou de um candidato a medicamento.

Se o estágio atual da tecnologia não permite ainda eliminar totalmente os testes com animais, isto se deve em grande parte à falta de interesse de muitos cientistas em encontrar alternativas, uma vez que sacrificar um animal é muito mais simples e rápido.

Alternativa ética

É claro que vários grupos de pesquisadores já se dedicam ao tema, sendo eles os grandes responsáveis pelo desenvolvimento das novas técnicas já disponíveis.

Mas esses cientistas mais éticos nunca tiveram seus esforços totalmente recompensados pela falta de apoio para que os testes alternativos fossem validados e aceitos.

O novo Centro Brasileiro de Validação de Métodos Alternativos (Bracvam) é o primeiro esforço coordenado feito no Brasil com essa finalidade.

O Bracvam vai se dedicar inteiramente ao desenvolvimento de métodos alternativos para a validação de pesquisas que não utilizem animais na fase de testes.

O Centro será instalado pela Fundação Oswaldo Cruz (Fiocruz), através do Instituto Nacional de Controle de Qualidade em Saúde (INCQS), com a colaboração da Agência Nacional de Vigilância Sanitária (Anvisa).

"De maneira organizada, vamos trabalhar os dados e organizar grupos de pesquisas para que novas metodologias sejam fomentadas e passem a ser métodos oficiais," afirmou Isabela Delgado, pesquisadora do INCQS.

Ciência sem sacrifício de animais

Vários países já proíbem não apenas o sacrifício dos animais, mas também a produção e a importação de produtos desenvolvidos com testes em cobaias.

Ao lado da questão ética do sofrimento das cobaias, as pesquisas que utilizam animais são vistas como menos refinadas do ponto de vista técnico científico.

Já se sabe, por exemplo, que os experimentos com animais não levam em conta aspectos caracteristicamente humanos das doenças, como os componentes cognitivos e emocionais envolvidos.

Há poucos dias, uma equipe demonstrou que os camundongos utilizados nas pesquisas sobre doenças do coração não representam um modelo adequado para as doenças cardíacas humanas - o que funciona no coração do camundongo não funciona no coração humano.

Ao lado disso, já há uma grande preocupação dentro da própria comunidade científica sobre a possibilidade da criação de quimeras, criaturas híbridas humano-animais.

"Buscamos mais avanço técnico, resultados mais confiáveis, menos susceptíveis a erros, de menor custo e de mais fácil difusão em outros países," disse Isabella. "Encontramos 14 pesquisas de métodos alternativos no país e nossa ideia é reunirmos essa capacitação, pesquisarmos juntos."

Validação de métodos alternativos

Segundo Eduardo Leal, também do INCQS, universidades públicas brasileiras e centros de produção de vacinas, como o Instituto Butantan e o Adolph Lutz, têm estudos para validação de métodos alternativos.

Mas, segundo ele, a participação da Anvisa é crucial para que essas novas metodologias sejam validadas e aceitas na regulamentação dos produtos.

A União Europeia proíbe desde 2004 a utilização de cobaias em linhas de desenvolvimento de artigos direcionados ao mercado da beleza.

Preocupados com essa tendência, algumas indústrias no Brasil também têm investido para abolir teste com animais na produção de cosméticos.

Alternativas ao uso de animais em pesquisas

Veja alguns resultados recentes divulgados pelo Diário da Saúde que evitam o sacrifício de animais nas pesquisas científicas:

• Cientista cria alternativa para o uso de animais no teste de medicamentos
• Fígado artificial vai substituir testes de medicamentos em animais
• Genoma do camundongo mostra deficiências de seu uso como modelo animal
• Boneca feita com células vivas poderá substituir modelos animais
• Pesquisa com animais não é mais necessária na era do genoma, diz associação
• O passado e o futuro das experiências com animais
• Europa restringe o uso de animais em pesquisas científicas
• Animais nas pesquisas científicas: até quando?

Descoberto processo natural que elimina o colesterol

O processo facilita a remoção do colesterol e pode representar um alvo totalmente novo para reverter a aterosclerose, a principal causa de ataque cardíaco e derrame.

Autofagia

Cientistas da Universidade de Ottawa, no Canadá, descobriram que uma rota bioquímica bem-conhecida, chamado autofagia, também mexe com o colesterol e pode ser responsável por enviá-lo para fora das células.

O Dr. Yves Marcel e seus colegas demonstraram que a autofagia - que significa auto-digestão - é responsável por "engolir e digerir" o colesterol acumulado nas paredes das artérias.

Esse processo facilita a remoção do colesterol e pode representar um alvo totalmente novo para reverter aaterosclerose, a principal causa de ataque cardíaco e derrame.

Acúmulo do colesterol

Há uma necessidade urgente de compreender como a acumulação de colesterol nas artérias pode ser revertida, dada a incidência cada vez maior dos problemas que ele causa.

O colesterol se acumula nas paredes das artérias, podendo causar a aterosclerose, também conhecida como estreitamento das artérias, o que provoca bloqueios e reduz o fluxo sanguíneo para o coração. Isso muitas vezes culmina em ataques cardíacos e derrames.

"A constatação de que a autofagia também funciona para digerir e liberar o colesterol das células e o fato de que sabemos que esta via é regulada dá esperança para o desenvolvimento de novas drogas que possam ativar a exportação do colesterol das paredes das artérias", disse Marcel.

Importância do colesterol

O trabalho vem mostrar a enorme complexidade da bioquímica envolvendo o colesterol.

Já se sabe, por exemplo, que não é só a quantidade de colesterol bom que importa e que o colesterol ruim não é tão ruim quanto se pensava.

O colesterol é importante para a estrutura da célula.

Os problemas surgem quando colesterol demais é depositado dentro das paredes da artéria coronária - as origens da doença arterial coronariana.

Os pesquisadores agora estão investigando como este processo está envolvido no desenvolvimento da aterosclerose, um passo que pode ajudar os especialistas em medicina cardiovascular entender e encontrar uma nova maneira de deter a progressão da doença de coração.

• Médicos criam nova abordagem alimentar para diminuir o colesterol

Learning How Gut Bacteria Influence Health: Scientists Crack Sparse Genome of Microbe Linked to Autoimmunity

ScienceDaily (Sep. 14, 2011) — Scientists have deciphered the genome of a bacterium implicated as a key player in regulating the immune system of mice. The genomic analysis provides the first glimpse of its unusually sparse genetic blueprint and offers hints about how it may activate a powerful immune response that protects mice from infection but also spurs harmful inflammation.

A little-known bacterial species called segmented filamentous bacterium, or SFB, can activate the production of specialized immune cells in mice. This scanning electron microscope image of an SFB colony shows a mass of long hair-like filaments created when the bacteria stay attached to each other after they divide. 

The researchers, led by Dan Littman, the Helen L. and Martin S. Kimmel Professor of Molecular Immunology at NYU School of Medicine and a Howard Hughes Medical Institute Investigator, and Ivaylo Ivanov, PhD, of Columbia University Medical Center, published their findings in the September 15, 2011, issue of Cell Host and Microbe. The study suggests that the gut-dwelling microorganism, named segmented filamentous bacteria (SFB), is genetically distinct from all 1,200 bacterial genomes studied so far, reflecting its relatively unique role in the gut.

Although SFB was first identified more than 40 years ago, it wasn't until 2009 that Dr. Littman and an international team of collaborators discovered that it can recruit specialized T cells, called Th17 cells, in the small intestine of mice. These potent immune cells, they subsequently found, protected the mice from disease-causing Citrobacter rodentium bacteria, but also made them more susceptible to inflammation and autoimmune arthritis. Those initial results suggested other intestinal bacteria might also regulate immune function.

"What has become clear in the last couple of years is that individual bacteria can specifically influence particular branches of the immune system," says Dr. Littman. In the new study, his team deciphered SFB's 1.57 million letters of DNA, almost 2,000 times smaller than our own genome and about one-third the size of its closest relative.

The microbe's sparse genome lacks many genes needed for its own survival, such as ones for making amino acids and other essential nutrients. As a result, it is dependent on other gut-dwelling bacteria or its host for food, according to the study. The examination of its 1,500 genes, however, suggests it is well adapted to the small intestine, where it clings to the thin lining and may help prevent other microbes from breaching the barrier.

Although the study didn't uncover any definitive signs of the SFB living within us, Dr. Littman suspects the resourceful bacteria have adapted to certain human populations. Even if it isn't found in our intestinal tract, scientists could apply what they have learned to obtain insights into the function of similarly acting microorganisms within us.

"Maybe in humans, there is another bacterium that is different from SFB but behaves functionally in the same way," says Dr. Ivanov, who conducted the latest analysis as a postdoctoral researcher in Dr. Littman's lab.

Recently, Japanese researchers found intestinal bacteria in humans that can boost development of regulatory immune cells in mice, thereby keeping the inflammatory activity of Th17 cells in check. Dr. Littman and his NYU collaborators may have also uncovered a microbe in the intestinal tract of rheumatoid arthritis patients that alters immune function. These emerging results underscore the need to understand how the microbes living in our bodies may impact our health.

"This research brings us the potential genetic mechanisms that trigger differentiation of Th17 cells which we have long believed to have a strong role in the development of autoimmune diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and Crohn's disease," said Steven Abramson, MD, professor, Departments of Medicine and Pathology and director of the Rheumatology Division at NYU Langone Medical Center. "With more than 50 million Americans suffering from at least one autoimmune disease, this research gives scientists and clinicians a greater ability to apply knowledge gained in the laboratory to actual clinical cases, moving it from 'bench-to-beside' to give patients a tremendous advantage and physicians the ability to fine-tune medications and protocols based on patient response."

Study of Metabolites Reveals Health Implications from Small Molecules

ScienceDaily (Sep. 14, 2011) — Researchers have undertaken the most comprehensive investigation of genetic variance in human metabolism and discovered new insights into a range of common diseases. Their work has revealed 37 new variants that are associated with concentrations of metabolites in the blood. Many of these match variants associated with diseases such as chronic kidney disease, type 2 diabetes and blood clotting.

Genetic basis of human metabolic individuality. The 37 genetically determined metabotypes (GDMs) explain a highly relevant amount of the total variation in the studied population and therefore contribute substantially to the genetic part of human metabolic individuality. a. GGDMs are shown colour coded by general metabolic pathways, together with selected associated metabolic traits, highlighting the relationship between gene function and the associated metabolic trait. b. GDMs are presented here colour coded by general metabolic pathways together with selected associated metabolic traits, highlighting the relationship between gene function and the associated metabolic trait metabolic trait GDMs are colour-coded by overlap with associations in previous GWAS with disease (red), intermediate risk factors for disease (yellow) and other traits (green). 

The team conducted the largest ever study of the human genome for genetic variants associated with metabolites -- the biochemical compounds representing the start or end of metabolic reactions -- using genome wide association analysis. They were searching for genetic influences on levels of more than 250 compounds in people's blood, including lipids, sugars, vitamins, amino acids and many others. They discovered variants that have a significant effect on the levels of these compounds, and hence on the underlying biological and disease processes.

"Our findings provide new insights for many disease-related associations that have been reported in previous studies, including cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, thrombosis and Crohn's disease," says Dr Nicole Soranzo, one of the study's researchers from the Wellcome Trust Sanger Institute. "Often the effects of variants discovered in genome wide association analyses are modest and we perhaps have a poor understanding of the biologic mechanism behind the association. Our approach can overcome these problems and possibly inform individualized therapy/treatment."

In previous studies, scientists have looked at the levels of one or a few metabolic traits; for example, cholesterol levels, or sugar in the blood, that is investigated in the doctor's surgery to help to diagnose disease. The new approach in this work was to assay a much wider range of smaller biochemical compounds, to give as complete a picture as possible of the molecules that are symptoms of disease and those that might contribute to disease.

The hope was that this more complete picture would allow researchers to better understand the function of genetic variants responsible for driving disease. This was the case.

Among the discoveries made by the team was a previously unknown association of mannose, a natural sugar, with diabetes-associated variants; this link suggests a new line of research to examine the role of mannose in diabetes, both as a diagnostic and as part of the disease process.

They also identified a possible mechanism to detoxify substances, which could affect the risk of developing kidney disease. This followed the discovery of a highly significant association with the NAT8 gene.

"These are remarkable findings powered by our method that enables researchers to identify new and potentially relevant metabolic processes and pathways," says Professor Karsten Suhre. Dr Christian Gieger adds: "To improve effectively treatment through biomedicine, we need to put genetics into its biological context. In trying to do this in our study, we have identified new molecules of interest that could be clinically significant." Both are the lead authors from the Helmholtz Center Munich, German Research Centre for Environmental Health.

Their study also discovered variants associated with blood clotting and thrombosis.

"We were able to show that variants in or near three genes are associated with a biochemical modification to peptides, a small protein that controls blood clotting. These same variants are variously associated with an increased risk for heart disease, thrombosis and other similar conditions," says Professor Tim Spector, Director of the TwinsUK twin cohort at the Department of Twin Research and Genetic Epidemiology, King's College London, which provided one of the two study samples. "We speculate that this is a new example of a mechanism that alters blood clotting. This discovery could one day lead to improved treatments."

Additionally, the researchers investigated the association of metabolite levels with drug response and treatment, including statins and thalidomide. They showed that in one case, a variant in a gene called ACE, associated with blood pressure control, could undermine treatment effects. The novel biochemical basis could help to identify possible side effects in drug trials and support development of new formulations to reduce side effects.

The data will be made publicly available as a knowledge-based resource on the internet to aid future studies, and biological, as well as clinical, interpretation of genome wide association studies.

Psychologists Discover Oxytocin Receptor Gene's Link to Optimism, Self-Esteem

ScienceDaily (Sep. 14, 2011) — UCLA life scientists have identified for the first time a particular gene's link to optimism, self-esteem and "mastery," the belief that one has control over one's own life -- three critical psychological resources for coping well with stress and depression.

Researchers have linked the oxytocin receptor gene to optimism, self-esteem and "mastery," the belief that one has control over one's own life -- three critical psychological resources for coping well with stress and depression.

"I have been looking for this gene for a few years, and it is not the gene I expected," said Shelley E. Taylor, a distinguished professor of psychology at UCLA and senior author of the new research. "I knew there had to be a gene for these psychological resources."

The research is currently available in the online edition of the journalProceedings of the National Academy of Sciences (PNAS) and will appear in a forthcoming print edition.

The gene Taylor and her colleagues identified is the oxytocin receptor gene (OXTR). Oxytocin is a hormone that increases in response to stress and is associated with good social skills such as empathy and enjoying the company of others.

"This study is, to the best of our knowledge, the first to report a gene associated with psychological resources," said lead study author Shimon Saphire-Bernstein, a doctoral student in psychology in Taylor's laboratory. "However, we wanted to go further and see if psychological resources explain why the OXTR gene is tied to depressive symptoms. We found that the effect of OXTR on depressive symptoms was fully explained by psychological resources."

At a particular location, the oxytocin receptor gene has two versions: an "A" (adenine) variant and a "G" (guanine) variant. Several studies have suggested that people with at least one "A" variant have an increased sensitivity to stress, poorer social skills and worse mental health outcomes.

The researchers found that people who have either two "A" nucleotides or one "A" and one "G" at this specific location on the oxytocin receptor gene have substantially lower levels of optimism, self-esteem and mastery and significantly higher levels of depressive symptoms than people with two "G" nucleotides.

The findings are "very strong, highly significant," Taylor said. The study has important implications.

"Sometimes people are skeptical that genes predict any kind of behavior or psychological state. I think we show conclusively that they do," said Taylor, who is a member of the National Academy of Sciences and directs UCLA's Social Neuroscience Laboratory.

She stresses, however, that while genes may predict behavior, they do not determine it.

Genes are not destiny

"Some people think genes are destiny, that if you have a specific gene, then you will have a particular outcome. That is definitely not the case," Taylor said. "This gene is one factor that influences psychological resources and depression, but there is plenty of room for environmental factors as well. A supportive childhood, good relationships, friends and even other genes also play a role in the development of psychological resources, and these factors also play a very substantial role in whether people become depressed.

"There is a genetic basis for these resources, but no -- the OXTR gene does not explain most of these resources. The more you study genes, the more you realize that many factors influence their expression."

"The expression of genes is not always stable," Saphire-Bernstein noted. "For physical features like eye color, it is stable. Your eye color is not going to change this week, but your depression might change this week. Genes are only one set of contributing factors to behavior, to illness and to psychological disorders such as depression."

The researchers brought 326 people into a UCLA laboratory and had them complete self-assessments of optimism, self-esteem and mastery. To measure self-esteem, questionnaires included such statements as "I feel I am a person of worth, at least as much as other people" and asked subjects whether they agreed or disagreed, using a four-point scale. To measure optimism, the researchers included statements such as "In uncertain times, I usually expect the best" and "I hardly ever expect things to go my way."

The researchers obtained DNA from participants' saliva and used UCLA's Genotyping Center to analyze the DNA for the variants in the OXTR gene. Participants also completed an assessment of depression, using a tool that is often employed by clinical psychologists to identify people at risk for mental health problems.

"People with the 'A' variant scored substantially higher on depression. The question is whether that association between the gene and depression is explained by psychological resources," said Taylor, a founder of the field of health psychology who was honored last year with the American Psychological Association's Lifetime Achievement Award. "We found the answer is yes. The relation of the gene to depression is explained entirely by these psychological resources."

Even people with the "A" variant can overcome depression and manage stress, according to Taylor. "We found nothing that interferes with learning coping skills," she said.

The research implies that people would benefit if they could train themselves to be more optimistic, to have higher self-esteem and a higher sense of mastery to improve their ability to cope with stressful events.

The research was federally funded by the National Science Foundation and by the National Institutes of Health's National Institute on Aging.

Other co-authors of the study were Baldwin Way, an assistant professor of psychology at Ohio State University who conducted the research as a UCLA postdoctoral scholar in Taylor's lab, and Heejung Kim and David Sherman, associate professors of psychology at UC Santa Barbara, who are also former members of Taylor's lab.

An increase in oxytocin tends to lead to more social behavior, especially under stress and especially in females, earlier research has indicated.

OXTR likely interacts with other genes. Taylor and her colleagues plan to continue to search for additional genes that predict behavioral responses to stress and to study how they interact.

"I originally assumed that biology largely determines behavior, and so it was a tantalizing surprise to see how clearly social relationships forge our underlying biology, even at the level of gene expression," Taylor wrote in her 2002 book "The Tending Instinct: How Nurturing Is Essential to Who We Are and How We Live." "Chief among these social forces are the ways in which people take care of one another and tend to one another's needs. An early warm and nurturant relationship, such as mothers often enjoy with their children, is as vital to development as calcium is to bones.

"The benefits that tending provides to children, especially those with genetic risks, are substantial. From life in the womb to the surprisingly resilient brain of old age, the social environment molds and shapes the expression of our genetic heritage until the genetic contribution is sometimes barely evident. A mother's tending can completely eliminate the potential effects of a gene; a risk for a disease can fail to materialize with nurturing, and a genetic propensity may lead to one outcome for one person and the opposite for another, based on the tending they received."

Evolution of a Gene Provides a Possible Explanation for the Development of Metastases and Mental Retardation

ScienceDaily (Sep. 14, 2011) — In the course of examining the Drosophila tumor suppressor gene (Dlg), scientists at the Helmholtz Zentrum München have succeeded in decoding a new mechanism that regulates cell polarity in epithelial tissues or in neurons in the brain. The findings, which are presented in the current issue of Developmental Cell, will help to enhance the understanding of how metastases and mental retardation occur and enable targeted, long-term therapeutic approaches to their treatment to be developed.

Mutations of the Dlg tumor suppressor gene trigger cancer and metastases in fruit flies, and mental retardation in mammals. A team of scientists headed by Professor Heiko Lickert from the Institute for Stem Cell Research at the Helmholtz Center Munich working in cooperation with colleagues from the Department for Protein Analysis and the Institute for Toxicology has now discovered why the Dlg gene family has gained other evolutionary functions. Fruit flies possess a copy of the Dlg gene, which plays a role in regulating cell proliferation* and basolateral epithelial polarity. Mammals possess four copies of the Dlg gene which have developed in different ways. As a result of these changes, Dlg3* has assumed a new function. It is responsible for the apical alignment of cells* and acts as a structural protein to stabilize tight junctions*. This new function is due to minor changes in the sequence of amino acids of the protein produced by the Dlg3 gene. These promote interaction with other proteins and, as a result, make it possible to determine and maintain the alignment of the apical side of the cell.

In the event of a mutation, this new function of the Dlg3 gene in mammals could alter the tissue structure of the Spemann/Mangold organizer*, which plays a pivotal role in neural induction and normal brain development. Previous studies have shown that mutations in the human Dlg3 gene go hand-in-hand with mental retardation. The scientists could therefore have discovered the cause of this disorder, which also plays a decisive role in humans and which they could use as a target for new therapies and active substances. Follow-up studies will help to explain the mechanism in greater detail because "the more we know about the mechanisms that lead to the loss of cell polarity and the formation of metastases, the better able we will be to develop new approaches to therapies and active substances," Professor Lickert says.

Notes:

*Dlg gene: tumor suppressor that controls cell proliferation and cell polarity. If it is mutated, it causes neoplastic tumors, i.e. cells proliferate in an unregulated manner, lose their polarity and as a result metastasize. Fruit flies only possess a copy of the Dlg gene. In mammals, the Dlg gene family encompasses four genes.

*Cell proliferation: increase in cells through cell growth and cell division.

*Apical/ basal/ lateral cell polarity: local alignment of a cell in the epithelium. Apical refers to the outer layers, basal to the inner layers and lateral to the side layers. This is important because different functions are performed on different sides of a cell.

*Dlg3: tumor suppressor found in mammals. If this gene is mutated, it causes mental retardation. Dlg 3 stands for Discs large homolog 3, neuroendocrine DLG or synapse-associated protein 102. It is localized on the X chromosome.

*Tight junctions: junctions composed of membrane proteins that hold neighboring cells together and thus also stabilize the cell walls. Tight junctions close the gaps between cells and form a diffusion barrier. Intercellular exchange is possible between the proteins themselves.

* Spemann/Mangold organizer: a structure in the embryo during gastrulation that organizes the development of all the other cells, including neuronal structures.