Sinais de eletrocardiograma aprimoram tratamento de cardíacos

Pequenos sinais cardíacos descobertos em horas de gravações de eletrocardiogramas (ECG) podem ajudar na identificação de pacientes com risco de morte, aponta artigo publicado nesta quarta-feira na revista "Science Translational Medicine".

Especial da Semana do Coração

O estudo foi divulgado pelos pesquisadores da Universidade de Michigan, do MIT (Instituto Tecnológico de Massachussets), da Escola de Medicina de Harvard e do Hospital Brigham and Women's, de Boston.

As conclusões do estudo podem ajudar milhares de pacientes cardíacos, que seriam tratados no tempo adequado e teriam suas vidas salvas. Aproximadamente 1 milhão de pessoas têm ataques cardíacos a cada ano nos Estados Unidos.

Em certos grupos de idade, a cada quatro pacientes que sobrevivem ao ataque inicial, um morre por complicações no prazo de um ano, revela a Associação Cardíaca Americana.

"Os métodos atuais para avaliar se as vítimas de ataques cardíacos necessitam de tratamentos mais agressivos podem identificar os grupos de pacientes com alto risco de complicações. Porém, os métodos não evitam as mortes, errando em quase 70% dos casos", afirma Cessam Syed, professor assistente do Departamento de Engenharia Elétrica e Ciências da Computação na Universidade de Michigan.

Os pesquisadores usaram técnicas de prospecção de dados e aprendizagem para analisar os ECG contínuos de 24 horas de 4.557 pacientes que tinham sofrido ataques cardíacos. O eletrocardiograma mede a atividade do coração.

Após as analises, os pesquisadores determinaram que os sinais de ECG de muitos dos pacientes continham padrões erráticos similares e, que até agora, estavam sendo desprezados, ou simplesmente não detectados.

Atualmente, os médicos receitam tratamentos mais fortes somente após um ataque cardíaco, levando em consideração vários fatores, incluindo a saúde geral do paciente, seu histórico médico, os resultados de várias análises de sangue e um ecocardiograma.

O ecocardiograma, que é diferente do eletrocardiograma, usa o ultrassom para obter uma imagem do coração e medir a quantidade de sangue que esta circulando em cada palpitação.

Depois de um ataque cardíaco, os pacientes são vulneráveis a morte repentina devido a irregularidades no ritmo cardíaco. Isto pode ser evitado com remédios e com desfibriladores implantados, que administram as descargas elétricas e normalizam o ritmo cardíaco.

Agora, segundo o artigo, é difícil determinar quem necessita desses remédios e dos desfibriladores. A maioria dos pacientes que tem desfibrilador implantado, no final, não os necessitam, sendo que a maioria das pessoas que morrem por ataque cardíaco repentino não foi identificada como candidato para usar o aparelho nos exames atuais.

Syed utilizou uma das ferramentas mais antigas em cardiologia: o eletrocardiograma, que se mantém junto ao paciente de ataque cardíaco internado no hospital.

Esse ECG funciona de maneira contínua enquanto o paciente está hospitalizado. Os médicos, normalmente, observam estes dados em poucos segundos.

Com o novo método, os médicos observaram as variações nas batidas do coração em períodos prolongados, assim como as sequências específicas de mudança no ritmo cardíaco e as diferenças nos sinais de ECG de um paciente comparado com outros históricos clínicos similares.

Os cientistas comprovaram que as pessoas com ao menos uma das anormalidades tinham de duas a três vezes maiores probabilidades de morrer nos meses seguintes. Agora, ao agregar as três técnicas às atuais ferramentas de avaliação, os médicos puderam prever 50% das mortes com menos positivos falsos.

Abuso de tranquilizantes pode aumentar risco de Alzheimer

O consumo crônico de benzodiazepinas (tranquilizantes, soníferos) aumenta o risco de uma pessoa sofrer de Alzheimer, segundo os primeiros resultados de um estudo francês, divulgados na revista "Sciences et Avenir" (Ciência e Futuro).

Anualmente entre 16 mil e 31 mil casos de Alzheimer seriam provocados na França por tratamentos com BZD (benzodiazepinas) ou similares e seus genéricos: Valium, Temesta, Xanax, Lexomil, Stilnox, Mogadon, Tranxène, etc., noticia a revista em sua edição de outubro.

Em torno de 120 milhões de caixas são vendidas por ano. Na França são consumidos de cinco a dez vezes mais soníferos e ansiolíticos do que em seus vizinhos europeus, acrescentou a "Sciences et Avenir".

O encarregado do estudo, professor Bernard Begaud (Inserm/Universidade de Bordeaux), se referiu às constatações como "uma verdadeira bomba".

"As autoridades precisam reagir", acrescentou, em declarações à revista. Devem agir muito mais, se levarem em conta que "de nove estudos, incluindo o nosso, a maioria (seis) vai neste sentido de uma relação entre o consumo de tranquilizantes e soníferos durante vários anos e o Alzheimer", afirmou.

"É um sinal de alerta muito forte", enfatizou.

O estudo foi realizado com 3.777 indivíduos de 65 anos ou mais que tomaram BZD entre dois e dez anos.

"Ao contrário das quedas e fraturas causadas por estes medicamentos, os efeitos cerebrais não são imediatamente perceptíveis, tendo que se aguardar alguns anos para que surjam", disse o pesquisador.

"Se em epidemiologia é difícil estabelecer uma relação direta de causa e efeito, quando há uma suspeita, parece normal agir e tentar limitar as prescrições inúteis, que são muitas", afirmou.

O aumento do risco, entre 20% e 50%, pode parecer pouco em escala individual, mas não na escala da população, por causa do consumo destes medicamentos por idosos, destacou a revista.

Segundo o professor Begaud, no total, 30% dos maiores de 65 anos consomem BZD, uma proporção enorme, e na maioria das vezes de forma crônica.

As prescrições são, regularmente, limitadas a duas semanas para os hipnóticos e doze semanas para os ansiolíticos.

A forma como os BZD atuam no cérebro para aumentar este risco de demência continua um mistério.

Mas o problema já tinha sido mencionado em 2006 em um relatório do Gabinete Parlamentar de Políticas de Saúde sobre Remédios Psicotrópicos.

"Depois não se fez nada", criticou o especialista.

Pesquisadores desenvolvem vacina contra Aids com 90% de eficácia

Uma equipe de pesquisadores espanhóis criou um protótipo de vacina contra o HIV "muito mais potente" que os desenvolvidos até agora. Os testes conseguiram uma resposta imune para 90% das pessoas sadias que foram expostas ao vírus.

A descoberta foi apresentada nesta quarta-feira em entrevista coletiva pelos responsáveis pela pesquisa, Mariano Esteban, do Centro Nacional de Biotecnologia do Conselho Superior de Pesquisas Científicas da Espanha (CSIC), Felipe García, do Hospital Clínic de Barcelona, e Juan Carlos López Bernaldo de Quirós, do Hospital Gregorio Marañón de Madri.

Após manifestarem uma grande eficácia em ratos e macacos, os testes começaram a ser aplicados em seres humanos há cerca de um ano. Nesta primeira fase, a vacina foi aplicada em 30 pessoas sadias, escolhidas entre 370 voluntários.

Durante o teste, seis pessoas receberam placebo e 24 a vacina. Estas últimas apresentaram "poucos" e "leves" efeitos secundários (cefaleias, dor na zona da injeção e mal-estar geral). Por isso, é possível afirmar que "a vacina é segura para continuar com o desenvolvimento clínico do produto", ressaltou Quirós.

Em 95% dos pacientes, a vacina gerou defesa (normalmente atinge 25%) e, enquanto outras vacinas estimulam células ou anticorpos, este novo protótipo "conseguiu estimular ambos", destacou Felipe García.

Para completar, em 85% dos pacientes as defesas geradas se mantiveram durante pelo menos um ano, "que neste campo significa bastante tempo", acrescentou.

Na próxima etapa, os pesquisadores realizarão um novo teste clínico, desta vez com voluntários infectados pelo HIV. O objetivo é saber se o composto, além de prevenir, pode servir para tratar a doença.

"Já provamos que a vacina pode ser preventiva. Em outubro, vacinaremos pessoas infectadas com HIV para ver se serve para curar. Geralmente, os tratamentos antirretrovirais (combinação de três remédios) devem ser tomados rigorosamente, algo insustentável em lugares tão afetados pela Aids como a África", apontou García.

O protótipo da vacina, batizado como MVA-B, recebe o nome do vírus Vaccinia Modificado Ankara (MVA, na sigla em inglês), um vírus atenuado que serve como modelo na pesquisa de múltiplas vacinas

Até agora, o único teste de vacina contra o HIV que chegou à terceira fase foi realizado na Tailândia. As duas primeiras fases testam a toxicidade do composto e sua eficácia, enquanto a terceira e a quarta examinam a posologia do remédio.

O protótipo da vacina, patenteado pelo CSIC espanhol, está sendo elaborado para combater o subtipo B do vírus da Aids, de maior prevalência na Europa, Estados Unidos, América Central e do Sul, além do Caribe. Na África e Ásia, o vírus mais comum é o subtipo C.

HIV alterado não consegue fugir do sistema imunológico

Enganando o enganador

Pesquisadores modificaram o HIV de tal forma que ele se tornou incapaz de enganar osistema imunológico humano.

Os resultados podem representar a remoção de um grande obstáculo para o desenvolvimento de uma vacina contra o HIV ou para o desenvolvimento de novos tratamentos para a AIDS.

"Alguma coisa no vírus HIV desliga a resposta imunológica, em vez de acioná-la, tornando-o um alvo difícil para o desenvolvimento de uma vacina", explica o Dr. David Graham. da Universidade Johns Hopkins, nos Estados Unidos.

"Parece que agora nós temos uma forma de contornar essa barreira," acrescenta.

Colesterol do vírus

Normalmente, quando as células do sistema imunológico encontram um vírus, elas disparam um alarme liberando substâncias químicas chamadas interferons, para alertar o resto do corpo da presença de uma infecção viral.

Quando as células imunológicas encontram o HIV, no entanto, elas liberam interferons demais, ficando sobrecarregadas e desligando a resposta subsequente de combate ao vírus.

Estudos anteriores mostraram que, quando células do sistema imunológico humano - os glóbulos brancos - estão com um nível baixo de colesterol, o HIV não consegue mais infectá-las.

Acontece que a cobertura que envolve e protege o genoma viral também é rica em colesterol, levando a equipe a pesquisar se os vírus sem colesterol ainda poderiam infectar as células, qualquer que fosse seu nível de colesterol.

Resposta imunológica inata

Os pesquisadores então trataram o HIV com um produto químico para remover o colesterol do seu revestimento viral.

Em seguida, eles introduziram, ou o HIV com baixo colesterol, ou o HIV normal, em células do sistema imunológico humano cultivadas em laboratório, e observaram como as células responderam.

As células expostas ao HIV com colesterol diminuído não liberaram qualquer interferon como resposta inicial, enquanto as células expostas ao normal HIV agiram normalmente, liberando interferon.

"O HIV alterado não sobrecarregou o sistema e, em vez disso, desencadeou a resposta imunológica inata, como acontece com qualquer primeiro encontro com um vírus," conta Graham.

Resposta imunológica adaptativa

Em seguida, os pesquisadores checaram se o HIV com baixo colesterol ativaria a chamada resposta imunológica adaptativa - a resposta que ajuda o corpo a se lembrar de patógenos específicos, para que o corpo desenvolva imunidade e se defenda de futuras infecções.

Elas não esperavam que o sangue HIV-positivo respondesse a qualquer uma das duas versões do HIV por conta dos grandes danos presentes no sistema imunológico dos pacientes HIV-positivos.

No entanto, quando o HIV com baixo colesterol foi introduzido no sangue imunologicamente deprimido, mas não-infectado pelo HIV, em um tubo de ensaio, as células da resposta imune adaptativa reagiram contra o vírus.

Alterando o vírus, explica Graham, foi possível acordar a resposta do sistema imunológico contra o HIV e ignorar as propriedades imunossupressoras do HIV.

"Além de aplicações nas pesquisas de vacinas, este estudo abre a porta para o desenvolvimento de drogas que ataquem o revestimento viral do HIV como uma terapia auxiliar para promover a detecção do vírus pelo sistema imunológico," diz Graham.

New Research Promises Better Collection of Prostate Cancer Cells

ScienceDaily (Sep. 28, 2011) — At the Oct. 2-6 microTAS 2011 conference, an international event for reporting research in microfluidics, nanotechnology and detection technologies for life science and chemistry, University of Cincinnati researchers will present a simple, low-cost, method for separating and safely collecting concentrated volumes of fragile prostate cancer cells.

This image shows the size dependence of particle trapping using fluorescent particles. The superimposed fluorescent image indicates trapping of larger particles (blue traces) while smaller particles (yellow traces) pass through. 

The research results resolve the critical technical challenge of isolating and collecting fragile cells, specifically rare circulating tumor cells (CTCs) that are present in the blood in very low concentrations -- as low as one cell in 100,000.

Normally, the isolation and collection of such cells is complicated and relies on the availability of biological markers on the cells; whereas, the method developed at UC -- using inertial microfluidic lab-on-a-chip technology -- is simple, relying only on cell size for separation. UC has already obtained a provisional patent for the new inertial microfluidics device and is in the process of obtaining a full patent.

At the Fifteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS) to be held Oct. 2-6, in Seattle, Wash., the research will be presented in papers titled "Extraction and Enrichment of Rare Cells in a Simple Inertial Microfluidic Device" and "Sorting Human Prostate Epithelial (HPET) Cells in an Inertial Microfluidic Device."

The first paper is by UC researchers Jian Zhou, engineering doctoral student, Premkumar Vummidi Giridhar, environmental health postdoctoral fellow; Susan Kasper, associate professor of environmental health; and Ian Papautsky, associate professor of engineering and director of both the

BioMicroSystems Lab and the Micro/Nano Fabrication Engineering Research Center at UC. The second paper is presented by Nivedita Nivedita, doctoral student in engineering, and by Giridhar, Kasper and Papautsky.

Kasper has been investigating the cancer stem cell properties of HPET cells and began collaborating with Papautsky to characterize prostate cancer stem cells and determine the manner in which these cells survive in the circulation and metastasize to their target organs such as bone. "Prostate cancer cells are a challenge to collect because they appear quite fragile and are present in very small numbers in the blood. If we damage them in the collection process, they are not viable for experimentation and the development of more effective strategies to combat this disease," Kasper adds.

General Background On Inertial Microfluidics: Spiral and Straight Channels

Inertial microfluidic lab-on-a-chip devices -- whether based on a straight or a spiral channel -- take advantage of hydrodynamic (liquid in motion) forces acting on cells or particles within laminar flow (fluid flows in parallel layers). These forces cause cells to equilibrate in streams near channel walls. The equilibrium positions of focused cells are strongly dependent on cell size, as well as flow properties and channel geometry. In spiral microchannels, these inertial forces can be influenced by centrifugal forces, adding additional control over the position of the focused streams of cells.

UC's work with inertial microfluidics -- both spiral and straight channel -- is unusual because, up until now, it has proven difficult to separate cells without the introduction of external electric or magnetic forces or using immunoselection.

How Inertial Microfluidic Chips Work

In spiral-channel lab-on-chips, a sample is introduced at the center of the spiral channel. Before the cells reach the end of the spiral, the cells focus into individual steams and are separated. Papautsky previously developed these chips for separating blood and other cell types at high throughput.

However, while successful, spiral chips are not able to separate out cells present in blood in extremely low concentrations, as is the case with prostate cells. This led him to explore inertial chips with straight channel geometries.

In a straight-channel inertial chip, a sample is introduced into a channel (with the diameter of a human hair) by means of a syringe. Before the cells reach the "crossroads" or "expansion" in the channel, lift and shear forces balance and focus cells into distinct groups near the sidewalls. This balance is disrupted at the "expansion" or "crossroads" and the larger cells, prostate cancer cells in this case, experience lateral velocity -- in other words, move sideways into the expansions where they are trapped for later use in experimentation.

This straight-channel method can be used to effectively isolate and collect cells and particles with a concentration as low as one cell per milliliter of blood.

According to UC's Papautsky, "The flow rate and channel geometry are critical to the method. We need to get the flow rate right so that the cells will separate out. We want to control the lift and shear forces that stem from the flow rate -- enough to cull out and collect the cancer cells but to avoid damaging them."

Method Has Broad Applications to Other Cell Types

While UC's experiments with inertial microfluidics focused on separating and concentrating prostate cancer cells, the approach is broadly applicable to other cell types and sizes. Working closely with Kasper, the Papautsky's group has already tested a number of other cell lines in these inertial microfluidic devices, including DU-145 cells (derived from brain metastasis) and LNCaP cells (derived from left supraclavicular lymph node). The simple planar structure of the devices and the passive mechanism of separation make them an easy-to-use tool for cell biologists, and affords integration with existing lab-on-a-chip systems.

This work was supported by the University of Cincinnati, the Defense Advanced Research Projects Agency (DARPA) N/MEMS S&T Fundamentals Program under a grant issued by the Space and Naval Warfare Systems Center Pacific to the Micro/Nano Fluidics Fundamentals Focus (MF3) Center to Ian Papautsky and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases to Susan Kasper.

How Normal Cells Become Brain Cancers

ScienceDaily (Sep. 28, 2011) — Brain tumor specimens taken from neurosurgery cases at the University of California, San Francisco (UCSF) Medical Center have given scientists a new window on the transformation that occurs as healthy brain cells begin to form tumors.

Representative NG2+ cell pairs from tumor and non-neoplastic tissue stained for NG2 and EGFR. Scale bars represent 10 μM.

The work may help identify new drugs to target oligodendroglioma, a common type of brain tumor, at its earliest stage, when it is generally most treatable. Any potential drugs identified will have to prove safe and effective in clinical trials, a process that can take several years.

As described in the journal Cancer Cell this month, the UCSF team found that the pool of cells from which oligodendroglioma tumors emerge normally divide "asymmetrically" by splitting into two unequal parts -- like giving birth to fraternal twins who look different and have distinct fates. When these normal cells transform into cancer cells, they switch gears and begin dividing symmetrically, essentially giving birth to identical twins instead.

"This happens early -- before the tumor forms, and it may provide a point to intervene in the process of tumor initiation," said Claudia Petritsch, PhD, an assistant professor with the UCSF Brain Tumor Research Center who led the research.

The Brain Tumor Research Center is part of the UCSF Department of Neurological Surgery, which is consistently ranked by U.S. News & World Report as one of the top departments in the world. Its doctors perform more than 1,100 neurosurgeries a year to remove brain tumors, and in the last 30 years, this work has helped to build one of the most extensive brain tumor repositories in the United States, with tissue samples collected from more than 7,800 cases of cancer.

In their research, Petritsch and her colleagues used genetically engineered mice to identify that a protein called NG2 controls this switch, and they are working on ways to target genes that regulate the process as a way of fighting oligodendroglioma and perhaps other brain tumors.

Why Divisions Matter to Cancer

Oligodendrogliomas are unusual among brain tumors because they often respond to chemotherapy drugs. However, the tumor frequently returns in a form that is resistant to chemotherapy and requires repeated surgical removal.

Petritsch and her colleagues first discovered last year that oligodendroglioma tumors derive from a type of progenitor cell called "oligodendrocyte progenitors" that proliferate in the brain throughout life. These progenitors may also play an important role when the brain is injured by multiplying rapidly and helping heal wounds.

The new studies in mice suggest that lacking an injury, these progenitors divide mostly asymmetrically, maintaining an equilibrium of these cells within the brain. Progenitors can also switch gears and divide symmetrically instead. Scientists believe that allows the brain to provide an expanded pool of cells when needed.

Using mouse models of the tumors as well as tissue samples taken from people with the disease, Petritsch and her colleagues showed that before the tumors arise, the cells preemptively make this switch, transforming from dividing asymmetrically to dividing symmetrically.

They used bioinformatics to discover that dozens of regulators of asymmetric cell division including NG2 are dysregulated in oligodendrogliomas. The Petritsch lab calls these "asymmetry proteins" and argues that if mutated they probably cause the switch to abnormal cell divisions and thereby initiate the genesis of tumors. Modulating NG2 and dysregulated asymmetry proteins pharmacologically may restore normal division modes and provide a new way to fight the cancer with drugs.

Correcting Sickle Cell Disease With Stem Cells

ScienceDaily (Sep. 28, 2011) — Using a patient's own stem cells, researchers at Johns Hopkins have corrected the genetic alteration that causes sickle cell disease (SCD), a painful, disabling inherited blood disorder that affects mostly African-Americans. The corrected stem cells were coaxed into immature red blood cells in a test tube that then turned on a normal version of the gene.

This digitally-colorized scanning electron micrograph (SEM) revealed some of the comparative ultrastructural morphology between normal red blood cells (RBCs), and a sickle cell RBC (left). 

The research team cautions that the work, done only in the laboratory, is years away from clinical use in patients, but should provide tools for developing gene therapies for SCD and a variety of other blood disorders.

In an article published online August 31 in Blood, the researchers say they are one step closer to developing a feasible cure or long-term treatment option for patients with SCD, which is caused by a single DNA letter change in the gene for adult hemoglobin, the principle protein in red blood cells needed to carry oxygen. People who inherited two copies -- one from each parent -- of the genetic alteration, the red blood cells are sickle-shaped, rather than round. The misshapen red blood cells clog blood vessels, leading to pain, fatigue, infections, organ damage and premature death.

Although there are drugs and painkillers that control SCD symptoms, the only known cure -- achieved rarely -- has been bone marrow transplant. But because the vast majority of SCD patients are African-American and few African-Americans have registered in the bone marrow registry, it has been difficult to find compatible donors, says Linzhao Cheng, Ph.D., a professor of medicine and associate director for basic research in the Division of Hematology and also a member of the Johns HopkinsInstitute for Cell Engineering. "We're now one step closer to developing a combination cell and gene therapy method that will allow us to use patients' own cells to treat them."

Using one adult patient at The Johns Hopkins Hospital as their first case, the researchers first isolated the patient's bone marrow cells. After generating induced pluripotent stem (iPS) cells -- adult cells that have been reprogrammed to behave like embryonic stem cells -- from the bone marrow cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques.

The researchers sequenced the DNA from 300 different samples of iPS cells to identify those that contained correct copies of the hemoglobin gene and found four. Three of these iPS cell lines didn't pass muster in subsequent tests.

"The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells," Cheng said.

In their process, his team converted the corrected iPS cells into immature red blood cells by giving them growth factors. Further testing showed that the normal hemoglobin gene was turned on properly in these cells, although at less than half of normal levels. "We think these immature red blood cells still behave like embryonic cells and as a result are unable to turn on high enough levels of the adult hemoglobin gene," explains Cheng. "We next have to learn how to properly convert these cells into mature red blood cells."

Only one drug treatment has been approved by the FDA for treatment of SCD, hydroxyurea, whose use was pioneered by George Dover, M.D., the chief of pediatrics at the Johns Hopkins Children's Center. Outside of bone marrow transplants, frequent blood transfusions and narcotics can control acute episodes.

The research was funded by grants from the Maryland Stem Cell Fund and the National Institutes of Health, and a fellowship from the Siebel Foundation.

Alzheimer's Protein Kills Nerve Cells in Nose; Animal Study May Suggest Way to Rescue Cells from Disease

ScienceDaily (Sep. 28, 2011) — A protein linked to Alzheimer's disease kills nerve cells that detect odors, according to an animal study in the Sept. 28 issue of The Journal of Neuroscience. The findings shed light on why people with Alzheimer's disease often lose their sense of smell early on in the course of the disease.

"Deficits in odor detection and discrimination are among the earliest symptoms of Alzheimer's disease, suggesting that the sense of smell can potentially serve as a 'canary in the coal mine' for early diagnosis of the disease," said Leonardo Belluscio, PhD, of the National Institute of Neurological Disorders and Stroke, who led the study. "The changes taking place in the olfactory system as a result of Alzheimer's disease may be similar to those in other regions of the brain but appear more rapidly" he added.

Researchers once thought that protein plaques commonly seen in the brains of people with Alzheimer's disease were responsible for killing off nerve cells, causing disruptions in memory -- a hallmark of the disease. The plaques are primarily derived from a protein called amyloid precursor protein (APP). The new study suggests that APP alone -- in the absence of the plaques -- may be to blame for the death of nerve cells.

In the new study, Belluscio and his colleagues genetically manipulated mice to produce high levels of a mutated version of human APP in olfactory nerve cells. The mutated form of the protein is seen in some people with early-onset Alzheimer's disease, a rare form that runs in families and strikes before age 65.

The researchers found that mice making mutant APP had four times as much olfactory nerve cell death by three weeks of age compared with normal mice. Although the cells that produced mutant APP died, the neighboring cells -- that did not have mutant APP -- survived. The cell death also occurred in the absence of amyloid plaques. Together, this showed that the cell death was initiated from within the cells making the mutant APP, not from plaques outside the cells. When the researchers blocked the olfactory nerve cells from producing high levels of the mutant precursor protein, more cells lived.

"Reducing APP production suppressed the widespread loss of nerve cells, suggesting that such disease-related death of nerve cells could potentially be stopped," Belluscio said.

"Together, these results support the hypothesis that amyloid proteins are involved in the degeneration of the brain that occurs with Alzheimer's disease," said Donald Wilson, PhD, of New York University School of Medicine and the Nathan Kline Institute for Psychiatric Research, an olfactory system expert who was unaffiliated with the study. "Further, they provide an exciting opportunity to explore how to prevent or reverse the events that lead to cell death and, ultimately, dementia."

Women Have Stronger Immune Systems Than Men -- And It's All Down to X-Chromosome Related microRNA

ScienceDaily (Sep. 28, 2011) — As anyone familiar with the phrase 'man-flu' will know women consider themselves to be the more robust side of the species when it comes to health and illness. Now new research, published in BioEssays, seems to support the idea. The research focuses on the role of MicroRNAs encoded on the X chromosome to explain why women have stronger immune systems to men and are less likely to develop cancer.

New research on the role of MicroRNAs encoded on the X chromosome helps explain why women have stronger immune systems to men and are less likely to develop cancer.

The research, led by Dr Claude Libert from Ghent University in Belgium, focused on MicroRNA, tiny strains of ribonucleic acid which alongside DNA and proteins, make up the three major macromolecules that are essential for all known forms of life.

"Statistics show that in humans, as with other mammals, females live longer than males and are more able to fight off shock episodes from sepsis, infection or trauma," said Libert. "We believe this is due to the X chromosome which in humans contains 10% of all microRNAs detected so far in the genome. The roles of many remain unknown, but several X chromosome-located strands of microRNA have important functions in immunity and cancer."

Dr Libert's team proposes that the biological mechanisms of the X chromosome have a strong impact on an individual's genes, known as genetic imprinting, which gives an immunological advantage to females. To develop their hypothesis the team produced a detailed map of all described microRNAs which have a role in immune functions and cancer in both human and mouse X chromosomes.

"We believe this immunological advantage is due to the silencing of X-linked genes by these microRNAs," said Libert. "Gene silencing and inactivation skewing are known mechanisms which affect X-linked genes and may influence X-linked microRNAs in the same way."

This genetic silencing leaves males at an immunological disadvantage as a male has only one X-chromosome. The Y-Chomosone contains fewer genes so if the genes involved in immunity are silenced maternally the male is left with no compensating genetic information.

"How this unique form of genetic inheritance influences X-chromosone linked microRNAs will be a challenge for researchers for years to come," concluded Libert, "not only from an evolutionary point of view, but also for scientists investigating the causes and cures of disease."