Câncer contagioso usa DNA do hospedeiro para consertar mutações

Tumor de cães é capaz de consertar sozinho suas mutações genéticas adotando genes do animal hospedeiro

Cientistas do Imperial College de Londres descobriram que uma forma peculiar de câncer contagioso - encontrado em cães, lobos e coiotes - pode consertar sozinha suas mutações genéticas adotando genes do animal hospedeiro. A descoberta pode ajudar a impedir a propagação de doenças semelhantes em outros animais e a compreender a progressão do câncer entre espécies. O estudo foi apresentado na última edição da revista Science.

Citologia do Tumor Venéreo Transmissível Canino

O Tumor Venéreo Transmissível Canino (TVTC) é uma forma muito pouco comum de câncer e é sexualmente transmissível, embora também possa se espalhar por lambidas ou mordidas na área afetada pelo tumor. As próprias células cancerosas passam de cão para cão, agindo como um parasita em cada animal infectado. Encontrado na maior parte das raças do mundo, os cientistas acreditam que o CTVT seja muito similar ao câncer observado nos demônios da Tasmânia.

No estudo, os pesquisadores britânicos revelaram o processo pouco comum que ajuda a célula cancerosa a sobreviver roubando pequenas "fábricas de energia" cheia de DNA das células dos animais infectados: as mitocôndrias. Elas então incorporam as mitocôndrias como se fossem suas próprias. A equipe de cientistas acredita que isso acontece por que os genes nas mitocôndrias do tumor têm a tendência a sofrer mutações.

Os resultados são surpreendentes pois as mitocôndrias - e seus genes - normalmente só são passadas de mãe para filho. Essa foi a primeira vez que a transferência mitocondrial entre células distintas foi observada ocorrendo na natureza.

Inicialmente o objetivo da pesquisa era entender como os cânceres encontrados em diferentes partes do mundo estão relacionados entre si, usando análise de DNA. No entanto, a equipe descobriu que o DNA do núcleo das células era diferente do DNA mitocondrial. Eles notaram que havia mais proximidade dos cânceres com os cães que com os outros cânceres. Foi esse dado que indicou o processo de adoção de mitocôndrias.

Os pesquisadores acreditam que o processo somente ocorra caso a célula cancerosa precise reparar suas próprias mitocôndrias. Um alta taxa de mutações genéticas leva a mitocôndrias não-funcionais nas células do TVTC, o que provoca uma perda de produtividade.

Em um estudo anterior os pesquisadores determinaram que o TVTC mais antigo surgiu em um cão ou lobo há 10 mil anos.

Estudo sueco investiga por que alguns diabéticos não têm complicações

Muitas pesquisas têm sido realizadas para descobrir os motivos pelos quais as pessoas com diabete desenvolvem complicações. Agora, cientistas fazem a pergunta inversa: eles querem saber por que alguns pacientes não têm essas complicações. O que é que os protege? O estudo Prolong (de "PROtetor da LONGevidade") pretende responder à questão.

Pesquisa piloto avalia quem é paciente há mais de 30 anos

"A maioria dos diabéticos, ao longo dos anos, desenvolve complicações graves ou fatais, mas entre 10% e 15% estão livres. Eles são os únicos em que estamos interessados", afirma Valeriya Lyssenko, que conduz o estudo juntamente com Peter Nilsson, ambos do Centro de Diabete da Universidade de Lund, na Suécia.

As principais complicações da diabete incluem doenças renais (nefropatias), lesões oculares (retinopatia), ataques cardíacos e derrames.

Artérias rígidas e açucaradas

Apesar de décadas de intensa pesquisa sobre as complicações da diabete, esses mecanismos fundamentais ainda não são totalmente conhecidos. Também não é possível prevenir ou tratar os danos aos vasos sanguíneos que atingem a maioria dos pacientes.

O risco de morrer de doenças cardiovasculares é de duas a três vezes maior para os doentes do que para os não-doentes. Os pequenos vasos sanguíneos também são prejudicados. Depois de apenas 10 anos com diabete, 70% das pessoas terão algum tipo de dano renal que poderá progredir para insuficiência. Como muitos sofrem de complicações oculares, alguns desenvolvem deficiência grave e 2% ficam cegos.

"Os vasos sanguíneos e outros órgãos do corpo tornam-se revestidos de açúcar e rígidos. É similar ao envelhecimento biológico precoce", compara Nilsson.

Metade dos "veteranos"

Talvez a própria natureza possa responder à pergunta de por que alguns pacientes são protegidos. Hoje existem cerca de 12 mil pessoas na Suécia com diabete há mais de 30 anos, das quais 1.600 têm a doença há mais de 50 anos.

"Cerca de metade desses 'veteranos' não têm maiores complicações. Dois terços dos que têm essa condição há mais de 50 anos escaparam de problemas relacionados. É claro que essas pessoas são diferentes e queremos saber o que é que as protege", afirma Valeriya.

Maior risco passa depois de 30 anos

O levantamento piloto, na província sueca de Escânia, avalia pacientes com diabete há mais de 30 anos. Num estágio posterior, portadores serão recrutados em todos os hospitais e centros de saúde do país. Eles serão comparados com os diabéticos que já desenvolveram complicações graves, apesar de terem a doença há menos de 15 anos.

O limite de 30 anos foi escolhido porque um indivíduo que tem diabete há muito tempo sem desenvolver complicações é improvável que apresente isso mais tarde.

Copiar os mecanismos de proteção da natureza

Os participantes vão responder a perguntas sobre sua vida e as doenças que eles ou seus parentes próximos apresentam. Várias amostras de sangue, incluindo testes genéticos, serão analisadas, e parentes dos voluntários também serão convidados a colaborar.

"Se pudermos identificar os fatores que protegem esses veteranos de complicações devastadoras, então pode ser possível desenvolver drogas que façam a mesma coisa", avalia Valeriya. 

Leptospirose é preocupação após enchentes

Recomendação é evitar ao máximo o contato com a água e o barro de enchentes e desmoronamentos

Além de perdas humanas e materiais, as chuvas que atingiram a Região Serrana do Rio de Janeiro trazem outro risco para a população: a leptospirose. Causada por uma bactéria presente na urina de animais, principalmente ratos, a doença pode levar a morte é comum em situações de enchente. A pesquisadora Ilana Teruszkin Balassiano, do Instituto Oswaldo Cruz (IOC/Fiocruz), aponta os cuidados que devem ser tomados pela população, ressalta a importância de higienizar bem pernas e pés e alerta que o risco da doença está presente tanto em áreas urbanas quanto em regiões afastadas de grandes centros.

A leptospirose é causada por bactérias do gênero Leptospira, presente na urina do rato, muito comum em esgotos de grandes cidades. No entanto, Ilana explica que ela também é excretada por outros animais, como bois, porcos e cachorros. "Por isso, em uma situação de enchente, a leptospirose continua a representar risco para a população, mesmo em áreas menos urbanizadas", afirma a especialista do Laboratório de Zoonoses Bacterianas do IOC, que atua como Referência Nacional para Leptospirose junto ao Ministério da Saúde e é reconhecido desde 2008 como Centro Colaborador da Organização Mundial da Saúde (OMS) para o agravo. 

A bactéria penetra no corpo pela pele, principalmente se houver alguma "porta de entrada", como um corte ou arranhão. Como pernas, pés e mãos estão mais expostos ao contato com lama e água que podem estar contaminados, os cortes e arranhões nestas localizações inspiram ainda mais cuidados. 

Segundo Ilana, porém, em situações como a vivida neste momento na Região Serrana fluminense, o contágio pode ocorrer pelo contato prolongado da água ou o barro contaminado com a pele, mesmo sem ferimentos. "Para diminuir os riscos, a recomendação é evitar ao máximo o contato com a água e o barro de enchentes e desmoronamentos. Se não for viável, lavar bem pernas, pés e mãos assim que possível", explica a especialista. "O uso de calça comprida e sapato fechado ajuda, mas não protege totalmente, pois acabam encharcados. O mais indicado é o uso de galochas ou sacos plásticos para proteger a pele por dentro do calçado, se não houver como evitar o contato com a água e o barro", orienta.

Ilana também indica cuidados na hora de voltar às residências atingidas por enchentes e desmoronamentos. "A Leptospira precisa de ambientes úmidos para sobreviver. Dessa forma, é importante evitar o contato com a lama das casas e terrenos, pois ainda há o risco de contaminação", explica. "A bactéria é sensível aos desinfetantes de forma geral, principalmente aqueles a base de cloro. Recomenda-se uma boa higienização das casas com esses produtos. 

Para lavar roupas atingidas pela enchente, por exemplo, o uso de água sanitária é indicado", explica. A pesquisadora destaca, ainda, a importância de orientar as crianças para evitar o contato com a água e a lama das casas e de consumir apenas água mineral ou devidamente tratada, para evitar o risco de contaminação por diversos microorganismos.

O período de incubação da leptospirose varia de cinco a dez dias. Os primeiros sinais da doença se assemelham a um resfriado, com febre, dores de cabeça e no corpo, especialmente na panturrilha, podendo ocorrer icterícia (coloração amarelada da pele e das mucosas). "Se a pessoa teve contato com a água das enchentes ou o barro de desmoronamentos e apresentar estes sintomas, deve procurar atendimento médico e relatar a situação, para que receba o tratamento adequado", explica Ilana.

A leptospirose é tratável, principalmente se diagnosticada logo, mas pode evoluir, em casos específicos, para formas mais graves, comprometendo os pulmões e os rins e causando a morte do paciente. O tratamento da doença é feito com antibióticos específicos e em casos mais graves pode ser necessária internação hospitalar.

Defense Mechanism Against Bacteria and Fungi Deciphered

ScienceDaily (Jan. 21, 2011) — To defend microbial attacks, the human body naturally produces a group of antibiotics, called defensins. An interdisciplinary team of biochemists and medical scientists has now deciphered the mechanism of action of a defensin, hitherto looked upon as exhibiting only minor activity. Their results might be useful in future drug development for inflammatory and infectious diseases. Nature now presents their findings online ahead of the print publication.

Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.

Under standard laboratory conditions, the human beta-defensin 1 (hBD-1), a human antibiotic naturally produced in the body, had always shown only little activity against microbes. Nevertheless the human body produces it in remarkable quantities. The solution to the puzzle was the investigation process itself, as the research group led by Dr. Jan Wehkamp at the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology of the Stuttgart-based Robert Bosch Hospital found out.

Before the research group took a new approach to this research, defensins were usually tested in the presence of oxygen, although little oxygen is present, for example, in the human intestine. Starting out from the discovery that a special antibiotic-activating protein of the human body is diminished in patients with inflammatory bowel diseases, Crohn's Disease and Ulcerative Colitis, the working group investigated how defensins act under low-oxygen conditions. During their investigations the scientists found out that under these conditions hBD-1 unfolds a strong antibiotic activity against lactic acid bacteria and yeast.

Furthermore the researchers discovered that another human protein, thioredoxin, is able to activate beta-defensin 1 even in the presence of oxygen. Moritz Marcinowski and Professor Johannes Buchner from the Department of Chemistry at the Technical University of Munich, used circular dichroism spectroscopy to elucidate the differences between the folded inactive and the unfolded active form of the protein.

Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.

So far the cause of inflammatory bowel disease is unclear. Genetic as well as environmental factors seem to play a role, finally leading to a weakening of the antimicrobial barrier, which is mainly mediated by defensins. Accordingly the identified mechanism might contribute to the development of new therapies to treat affected patients.

The presented work is the result of a cooperation project with six participating centers, led by Emmy Noether junior research group leader Dr. Jan Wehkamp. In addition to five researchers from Stuttgart (Dr. Margarete Fischer-Bosch-Institute for Clinical Pharmacology and the Robert Bosch-Hospital (Bjoern Schroeder, Sabine Nuding, Julia Beisner, Eduard Stange and Jan Wehkamp) the Department of Dermatology at University of Tübingen (Martin Schaller), the Max-Planck-Institute for Developmental Biology in Tübingen (Sandra Groscurth), the Department of Dermatology at University of Kiel (Zhihong Wu), as well as the Department of Chemistry at the Technische Universitaet Muenchen (Moritz Marcinowski and Johannes Buchner) were involved. The work was funded by the Deutsche Forschungsgemeinschaft (Emmy Noether-Program for young researchers, Cluster of Excellence Center for Integrated Protein Science Munich) and by the Robert- Bosch-Foundation.

Function of Novel Molecule That Underlies Human Deafness Revealed

ScienceDaily (Jan. 21, 2011) — New research from the University of Sheffield has revealed that the molecular mechanism underlying deafness is caused by a mutation of a specific microRNA called miR-96. The discovery could provide the basis for treating progressive hearing loss and deafness.

Left: Hair bundle morphology of immature inner hair cells (IHCs) from normal cochlea. Right: Hair bundle morphology of immature inner hair cells (IHCs) from diminuendo mutant mouse cochlea. (Credit: Image courtesy of University of Sheffield)

The research team, led by Dr Walter Marcotti, Royal Society University Research Fellow from the University's Department of Biomedical Science, in collaboration with Professor Karen Steel at the Sanger Institute in Cambridge, discovered that the mutation in miR-96 prevents development of the auditory sensory hair cells. These cells are located in the inner ear and are essential for encoding sound as electrical signals that are then sent to the brain.

The research has been published in the Proceedings of the National Academy of Sciences and was based on studies of mice, which do not normally hear until about 12 days after birth. Prior to this age their immature hair cells must execute a precise genetic program that regulates the development of distinct types of sensory hair cell, namely inner and outer hair cells.

The research teams found that in a strain of mice called diminuendo -- which carry a single base mutation in the miR-96 gene -- hair cell development is arrested around birth.

The study shows that miR-96 normally regulates hair cell development by influencing the expression of many different genes associated with a wide range of developmental processes at a specific stage. The researchers discovered that the mutation hinders the development not only of the mechanically sensitive hair bundle on the cell apex but also the synaptic structures at the base that govern transfer of electrical information to the sensory nerves. These new findings suggest that miR-96 is a master regulator responsible for coordinating the development of the sensory cells that are vital to hearing.

Since the mutation in miR-96 is known to cause human deafness and microRNA molecules can be targeted by drugs, the work also raises new opportunities for developing treatments to treat hearing loss.

Dr Walter Marcotti said: "Progressive hearing loss affects a large proportion of the human population, including new born and young children. Despite the relevance of this problem, very little is currently known regarding the genetic basis of progressive hearing loss. Our research has provided new and exciting results that further our understanding of auditory development as well as possible molecular targets for the development of future therapies."

The work was supported by the Royal National Institute for Deaf People (RNID), The Wellcome Trust and the University of Sheffield.

New Low-Cost Method to Deliver Vaccine Shows Promise

ScienceDaily (Jan. 21, 2011) — Researchers have developed a promising new approach to vaccination for rotavirus, a common cause of severe diarrheal disease that is responsible for approximately 500,000 deaths among children in the developing world every year.

In a study published in the November issue of Clinical and Vaccine Immunology, a vaccine delivered as nasal drops effectively induced an immune response in mice and protected them from rotavirus infection. The new vaccine delivery system has also been tested successfully and found to be heat stable with tetanus and is currently being tested with diphtheria and pertussis.

The team from the Cummings School of Veterinary Medicine at Tufts University and Tufts University School of Medicine collaborated with researchers from Boston and Tulane Universities to test the effectiveness of immunization with harmless bacteria that were engineered to display rotavirus protein.

"The new vaccine, in conjunction with an agent that enhances immunity, induced sufficient antibody formation against rotavirus to protect mice against infection when the mice were exposed to rotavirus three weeks after their third immunization," explained John E. Herrmann, PhD, research professor in the infectious diseases division of the department of biomedical sciences at the Cummings School of Veterinary Medicine at Tufts University and the senior author of the published study.

"We created the rotavirus vaccine using a harmless bacterium called Bacillus subtilis (B. subtilis), which we can modify to display on its surface or in its cytoplasm proteins from infectious bacteria and viruses. When people are exposed to these proteins, they develop antibodies against them and therefore become immune to the bacteria and viruses," said the study's first author Sangun Lee, PhD, DVM, research associate at the Cummings School. "The B. subtilis bacteria are so harmless that they are part of the normal diet in several Asian countries."

"The vaccine with the Bacillus bacteria is very inexpensive to produce in large quantities and, unlike most traditional vaccines, requires no special purification steps before use. As a result, the cost of vaccine production is unusually low," explained Saul Tzipori, BVSc (DVM), DSc, PhD, Agnes Varis University Chair in Science and Society, distinguished professor of microbiology and infectious diseases, and director of the infectious diseases division of the department of biomedical sciences at the Cummings School. These findings are consistent with the team's previous studies in which they demonstrated that B. subtilis bacteria displaying a fragment of tetanus toxin protein completely protect mice from tetanus. Tetanus vaccines have been stored for more than a year at 113ºF without any loss of potency, a property that may be common to all B. subtilis vaccines.

Vaccines currently available have to be stored in refrigerators or freezers until the moment they are administered. This cold chain is difficult and costly to maintain. In many parts of the world, there is insufficient refrigeration or electricity to keep vaccines cold. The lack of refrigeration combined with the lack of trained personnel, especially in rural areas in developing countries, make it impossible for many children and adults to be vaccinated against standard infections, such as tetanus, rotavirus, diphtheria, pertussis (whooping cough) and other diseases.

"In addition to being heat-stable and low-cost, the B. subtilisvaccines are given in the form of nasal drops or spray. A needle-free approach to vaccination is particularly advantageous in developing countries where clean needles and syringes and trained personnel are not always available," said team leader Abraham L. (Linc) Sonenshein, PhD, professor and acting chair of molecular biology and microbiology at TUSM and member of the genetics and microbiology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

"This vaccine project is still in the developmental stage," he continued. "The next major step for these vaccines is to show that they are safe and work well in humans, and then to extend the rotavirus and tetanus vaccine technology to include diphtheria, pertussis and other infectious diseases. Those diseases cause tens of thousands of deaths, particularly in newborns and in South-East Asia. We are actively looking for partners in the US and around the world to help us pursue our goal of reaching the point where many childhood and adult vaccines can be manufactured in a way that avoids the need for injection or refrigeration. Jerry Keusch of Boston University School of Public Health and I started this project 15 years ago and it has taken a long time to reach the stage where we now have effective needle-free vaccines. The technology has now advanced enough that we can expect to be successful with many other vaccines in a short time frame."

Additional authors include Boris R. Belitsky, PhD, assistant research professor in the department of molecular biology and microbiology at TUSM; James P. Brinker, M.P.H, in the department of biomedical sciences at the Cummings School; Kathryn O. Kerstein, MS, senior research associate in the department of molecular biology and microbiology at TUSM; David W. Brown, PhD, DVM, clinical assistant professor in the infectious diseases division of the department of biomedical sciences at the Cummings School; Gerald T. Keusch, MD, professor in the department of international health at Boston University School of Public Health, professor of medicine at Boston University School of Medicine and U.S. chairman of the Indo-U.S. Vaccine Action Program at the National Institutes of Health; and John D. Clements, PhD, professor and chair of the department of microbiology and immunology at Tulane University Health Sciences Center.

This study was supported by a grant from the Grand Challenges in Global Health program of the Bill and Melinda Gates Foundation, and this grant was administered by the Foundation for the National Institutes of Health. Patent applications related to the discoveries reported in these studies have been filed by Tufts University.

New Mechanism for Controlling Blood Sugar Level Discovered

ScienceDaily (Jan. 21, 2011) — Medical scientists at the University of Leicester have identified for the first time a new way in which our body controls the levels of sugar in our blood following a meal.

This hematoxylin- and eosin-stained pancreatic slice illustrates an islet of Langerhans adjacent to a capillary. (Credit: University of Leicester)

They have discovered the part played by a particular protein in helping to maintain correct blood sugar levels.

The breakthrough was made in the University of Leicester by a team led by Professor Andrew Tobin, Professor of Cell Biology, who is a Wellcome Trust Senior Research Fellow. The research is published online ahead of print in the international scientific journal theProceedings of the National Academy of Sciences.

Professor Tobin said: "The work, which was done wholly at the University of Leicester, is focused on the mechanisms by which our bodies control the level of sugar in our blood following a meal.

"We found that in order to maintain the correct levels of sugar, a protein present on the cells that release insulin in the pancreas has to be active. This protein, called the M3-muscarinic receptor, is not only active but also needs to undergo a specific change. This change triggers insulin release and the control of blood sugar levels."

Professor Tobin added: "Without the change in the M3-muscarinic receptor protein sugar levels go up in the same way that we see in diabetes. We are of course testing if the mechanism of controlling sugar levels we have discovered is one of the mechanisms disrupted in diabetes. If this were the case then our studies would have important implications in diabetes."