03 April 2012

La incidencia de cáncer de piel aumenta entre los jóvenes

Los propios autores del estudio se han sorprendido con los resultados. Lejos de reducirse, la tasa de cáncer de piel aumenta, especialmente entre quienes aún no han cumplido los 40 años. Así lo revelan los datos de un trabajo realizado en la Clínica Mayo (Rochester, Minnesota, EEUU), de los que también se concluye que las mujeres son las más 'castigadas' por esta enfermedad.
En línea con lo que otras investigaciones apuntaban, "ya imaginábamos que encontraríamos un incremento de casos, pero no que superarían a los que indica el Instituto Nacional de Cáncer de EEUU (NCI, en sus siglas en inglés)", argumentan los responsables del nuevo trabajo que acaba de publicar la revista 'Mayo Clinic Proceedings'. En particular, les ha llamado la atención la importante incidencia en las mujeres entre los 20 y los 30 años.
Después de revisar una base de datos de Olmsted (Minnesota, EEUU) con los primeros diagnósticos de melanoma en pacientes de 18 a 39 años entre 1970 y 2009, el principal líder de la investigación, Jerry Brewer y su equipo, observaron que la incidencia de melanoma aumentaba ocho veces entre las mujeres y cuatro veces entre los hombres.
Un panorama muy similar al español. "De hecho, en la Academia Andaluza de Dermatología se ha hecho un estudio sobre el cáncer de piel en el que se concluye no sólo que no se ha detenido la incidencia (como esperábamos a principios de los '90 con las campañas de prevención) sino que ha aumentado, sobre todo en los jóvenes y más en mujeres", argumenta Julián Conejo-Mir, jefe de Servicio de Dermatología del Hospital Universitario Virgen del Rocío de Sevilla.

Donde no da el sol

"Algo (además del sol como principal causa) está pasando", remarca el especialista español. Ya hay estudios, continúa, que señalan como culpables a las "mutaciones en los genes BRAF, NRAS y KIT". Esto explicaría los casos donde el cáncer de piel aparece en "localizaciones donde no da el sol, como los genitales, detrás de la oreja, etc". Lo que no se sabe es "qué es lo que está haciendo que estas mutaciones aumenten y en esta línea se está investigando en todo el mundo". Y añade: "Llevamos 30 años haciendo campañas de prevención solar y la incidencia del cáncer de piel sigue aumentando, algo se nos escapa".
Los investigadores del estudio estadounidense señalan las cabinas de bronceado como clave en el incremento de esta enfermedad, sobre todo en mujeres. "Un reciente estudio decía que los usuarios de estas camas tienen un 74% más de riesgo de desarrollar melanoma y sabemos que esta práctica les gusta más a ellas que a ellos". Sin embargo, a pesar de la abundante información que se ofrece a la sociedad al respecto, "siguen acudiendo a estas cabinas".
Dados los resultados de "nuestro estudio, se deberían desarrollar intervenciones que consigan reducir factores de riesgo de este tipo, que continúen subrayando los efectos carcinógenos de las camas de bronceado y recuerden la importancia de someterse a revisiones dermatológicas, sobre todo cuando se noten cambios y lesiones en la piel", concluye Bewer.
Precisamente este año, uno de los objetivos de la próxima campaña de cáncer de piel de la Academia Española de Dermatología y Venereología (AEDV) "serán las cabinas de rayos UVA", adelanta el doctor Conejo-Mir.

**Publicado en "EL MUNDO"

New Immune Defense Enzyme Discovered

Neutrophil granulocytes comprise important defences for the immune system. When pathogenic bacteria penetrate the body, they are the first on the scene to mobilise other immune cells via signal molecules, thereby containing the risk. To this end, they release serine proteases – enzymes that cut up other proteins to activate signal molecules. Scientists at the Max Planck Institute of Neurobiology in Martinsried have now discovered a new serine protease: neutrophil serine protease 4, or NSP4. This enzyme could provide a new target for the treatment of diseases that involve an overactive immune system, such as rheumatoid arthritis.
The functioning of the immune system is based on the complex interplay of the most diverse cells and mediators. For example, neutrophil granulocytes (a group of specialized white blood cells) react to bacteria by releasing substances called serine proteases. These enzymes are able to activate signal molecules, such as the chemokines, by cleaving them at a specific position on the molecule. The active signal molecules then guide other immune cells to the focus of inflammation in order to destroy the pathogens.
A research team led by Dieter Jenne at the Max Planck Institute of Neurobiology in Martinsried has come across a previously unknown protease in humans: neutrophil serine protease 4, or NSP4. "The special thing about this enzyme is that it cuts proteins that have the amino acid arginine at a particular point", says Dieter Jenne, research group leader at the Martinsried-based Institute. "This is where NSP4 differs from the other three known neutrophil serine proteases, which are similar in molecular structure, but have a different recognition motif." The scientists may be able to harness this difference to develop an active substance that specifically inhibits NSP4, thereby reducing the immune reaction.
However, serine protease activity comes at a cost. The enzymes not only heal inflammations, but sometimes cause them in the first place. If too many immune cells are activated, they can use their arsenal of aggressive chemical weapons against the body's own tissues. A number of chronic inflammatory diseases are based on precisely this effect. As a result, scientists are searching for substances that can block the neutrophil proteases. To date, however, none of the substances tested have been developed into effective drugs.
"So far, we don't know the identity of the NSP4 substrate, but we assume they must be signal molecules", says Dieter Jenne. Activated chemokines can recruit a vast number of neutrophils, and their sheer quantity alone is enough to cause tissue damage. "Proteases sometimes act as accelerants and can even trigger a chronic inflammation quite independently of bacterial intruders. If we dampened down the defences, we could counteract this effect", explains the scientist.
In terms of evolutionary history, NSP4 is the oldest of the four known neutrophil serine proteases. Using gene sequences, scientists have shown that the enzyme has hardly changed through hundreds of millions of years of evolution from bony fish to humans. "That would indicate that NSP4 regulates a fundamental process", says Dieter Jenne.
The fact that the enzyme remained undiscovered until now is because it occurs at a much lower concentration than the other three proteases. The Max Planck scientists came across it while searching the human genome for genes that encode serine proteases. In the process, they noticed a previously unknown gene sequence. Natascha C. Perera, a member of the Martinsried research group and lead author of the study, managed to produce and examine the enzyme in its active, folded state.
If they are to establish NSP4 in the future as a possible target protein for anti-inflammatory drugs, the scientists must now examine its function in living organisms and discover whether blocking the enzyme has adverse effects. The scientists are working with the company Novartis to answer these questions in laboratory mice. "NSP4 inhibitors could be used in diseases like chronic arthritis or inflammatory skin diseases", says Dieter Jenne, "but first we have to test the long-term effects of these substances."

**Published in "SCIENCE DAILY"

Un estudio arroja dudas sobre la utilidad de los test genómicos

Al ritmo que avanza la técnica, es más que probable que dentro de pocos años (cada vez menos), cualquiera pueda secuenciar su propio genoma por unos pocos euros. Sin embargo, la utilidad real de estos test está en entredicho a juzgar por el último análisis que acaba de publicar la revista 'Science Traslational Medicine'.
Más allá del capricho de unos pocos, o de algunas experiencias en el terreno experimental, el análisis del genoma completo de un individuo está aún lejos de convertirse en una herramienta útil en la práctica clínica diaria.
Así lo advierten Bert Vogelstein y su equipo, del Instituto Howard Hughes (en Baltimore, EEUU), después de analizar a miles de gemelos cuyos datos están almacenados en bases de datos de Suecia, Dinamarca, Finlandia, Noruega y EEUU. "Gemelos idénticos comparten un genoma idéntico y, por tanto, los mismos factores genéticos de riesgo", explican los investigadores, que utilizaron un modelo matemático para predecir las probabilidades de cada par de individuos de padecer una lista de 24 patologías (cáncer, ictus, patologías cardiovasculares, neurológicas, autoinmunes...) en comparación con el riesgo medio de la población general.
Con este modelo predictivo, diseñado por el hijo del propio Vogelstein, la mayoría de sujetos obtuvo un resultado negativo para 23 de las 24 enfermedades; lo que no quiere decir, ni mucho menos, que estén cien por cien libres de riesgo de padecer alguna de ellas a lo largo de su vida.
"Por ejemplo, sólo un 2% de las mujeres que se someten a un análisis del genoma completo recibirá un resultado positivo para un posible cáncer de ovario a lo largo de su vida", explica otro de los firmantes, Kenneth Kinzler. Eso no quiere decir que el 98% de las mujeres tenga garantías de que no va a padecer la enfermedad a lo largo de su vida.
"Los test genómicos no son un sustituto adecuado de las actuales estrategias de prevención", advierte Vogelstein. De momento, pues, las pruebas de diagnóstico precoz y las recomendaciones de prevención, como no fumar, siguen siendo la norma de oro para reducir el riesgo de numerosas enfermedades.
A su juicio, algunos individuos podrían pensar erróneamente que no padecerán ciertas enfermedades si su genoma no advierte de ellas; lo que resta valor informativo a dichos análisis. "No se puede concluir que dichos test sean útiles o inútiles en un sentido absoluto; su utilidad dependerá de sus resultados, de cada individuo, de sus perspectivas... Y reconocer estas limitaciones será de gran utilidad para la industria, las compañías de seguros, las autoridades sanitarias y los consumidores", rematan.

**Publicado en "EL MUNDO"

Caloric Moderation Can Reverse Link Between Low Birth Weight and Obesity, Early Study Indicates

Babies who are born small have a tendency to put on weight during childhood and adolescence if allowed free access to calories. However, a new animal model study at UCLA found when small babies were placed on a diet of moderately regulated calories during infancy, the propensity of becoming obese decreased.

Because this is an early study, UCLA researchers do not recommend that mothers of low-birth weight infants start restricting their child's nutrition and suggest they consult with their child's pediatrician regarding any feeding questions.
Previous studies have shown that growth restriction before birth may cause lasting changes of genes in certain insulin-sensitive organs like the pancreas, liver and skeletal muscle. Before birth, these changes may help the malnourished fetus use all available nutrients. However, after birth these changes may contribute to health problems such as obesity and diabetes.
"This study shows that if we match the level of caloric consumption after birth to the same level that the growth-restricted baby received in the womb, it results in a lean body type. However, if there is a mismatch where the baby is growth-restricted at birth but exposed to plenty of calories after birth, then that leads to obesity," said the lead author, Dr. Sherin Devaskar, professor of pediatrics and executive chair of the department of pediatrics at Mattel Children's Hospital UCLA. "While many trials that include exercise and various drug therapies have tried to reverse the tendency of low birth weight babies becoming obese, we have shown that a dietary intervention during early life can have long lasting effects into childhood, adolescence and adult life."
The study appears in the June issue of the journal Diabetes and is currently available online.
About 10 percent of babies in the United States are born small, defined as less than the 10th percentile by weight for a given gestation period, said the study's first author, Dr. Meena Garg, professor of pediatrics and a neonatologist and medical director of the neonatal intensive care unit at Mattel Children's Hospital UCLA. She added that some organizations define low birth weight as less than 2,500 grams or 5 pounds, 5 ounces at term.
Low birth weight can be caused by malnutrition due to a mother's homelessness or hunger or her desire not to gain too much weight during pregnancy. Additional causes include illness or infection, a reduction in placental blood, smoking or use of alcohol or drugs during pregnancy.
To conduct the study, researchers used rodent animal models and simulated a reduced calorie scenario during pregnancy. The results showed that low-birth weight offspring exposed to moderately tempered caloric intake during infancy and childhood resulted in lean and physically active adults related to high energy expenditure, as opposed to unrestricted intake of calories, which resulted in inactive and obese adults due to reduced energy expenditure. The authors concluded that early life dietary interventions have far reaching effects on the adult state.
Future studies will follow this study over the stages of aging to see if early regulation of calorie intake reverses diabetes and obesity while aging.
"This is an early pre-clinical trial that first needs to be tested in clinical trials before any form of guidelines can be developed," Devaskar said. "More importantly, we must make sure that control of caloric intake during infancy and childhood does not have any unintended side effects before taking on clinical trials. More research is required to ensure that these metabolic advantages will persist later in life."

**Published in "SCIENCE DAILY"

Los españoles, reacios a controlar nuestro colesterol

El 68 por ciento de la población española no cambia sus hábitos de vida para prevenir el colesterol, uno de los principales factores de riesgo cardiovascular que podemos modificar y que afecta al 40 por ciento de las personas adultas. Así lo constata un estudio realizado por Ángel Díaz Rodríguez, coordinador del grupo de lípidos de la Sociedad Española de Médicos de Atención Primaria (SEMERGEN), quien asegura que es posible mantener a raya los niveles de esta sustancia si seguimos una dieta equilibrada, hacemos deporte o evitamos fumar.

Precisamente, el Día Mundial de la Salud, que se celebrará el próximo 7 de abril, se centra en el envejecimiento de la población y nos recuerda la importancia de cambiar nuestros hábitos de vida para mantener el colesterol a raya.
Dieta equilibrada

El colesterol aumenta con la edad pero, según Díaz Rodríguez, podemos actuar para hacernos mayores de forma saludable y evitar tener unos niveles elevados de esta sustancia. Para controlarlo, es recomendable una dieta que incluya frutas y hortalizas, productos lácteos reductores del colesterol, cereales integrales, legumbres, pescado, aceite de oliva y frutos secos.

También es saludable priorizar las cocciones a la plancha, al vapor o al horno, limitar la ingesta de alimentos con un alto contenido en grasas saturadas, volver a la dieta mediterránea y consumir productos lácteos reductores de esta sustancia. Además de una alimentación sana y equilibrada, para compensar y reducir el colesterol, también es importante practicar ejercicio físico de forma regular, según Meritxell Gómez, experta en nutrición y salud.

El colesterol alto o hipercolesterolemia no presenta síntomas ni signos físicos, pero diagnosticarlo es tan fácil como realizarse un análisis de sangre. Por ello, se recomienda determinar el nivel de colesterol al menos una vez antes de los 35 años en los varones y de los 45 años en mujeres.

Díaz cree que «hay que reforzar el control a partir de los 45 años en los varones y de los 55 años en las mujeres y acudir al médico de forma regular para conocer nuestros niveles de colesterol». El estudio apunta que más del 45% de los encuestados acude a su médico al menos una vez al año para determinar sus niveles de colesterol, y que los que no realizan controles periódicos alegan principalmente que, al sentirse bien, perciben no es necesario.

**AGENCIAS

Heart failure's effects in cells can be reversed with a rest

Structural changes in heart muscle cells after heart failure can be reversed by allowing the heart to rest, according to research at Imperial College London. Findings from a study in rats recently published in the European Journal of Heart Failure show that the condition's effects on heart muscle cells are not permanent, as has generally been thought. The discovery could open the door to new treatment strategies. Heart failure means that the heart muscle is too weak or stiff to pump blood as effectively as it needs to, and it is commonly the result of a heart attack. Around 750,000 people in Britain are living with heart failure. Severe heart failure carries a risk of death within one year which is worse than most cancers, and new heart failure treatments are badly needed.
Patients with advanced heart failure are sometimes fitted with a left ventricle assist device (LVAD). The LVAD is a small pump that boosts the function of the heart and reduces strain on the left ventricle, the biggest chamber of the heart, which pumps blood around the body's main circulation.
In 2006, researchers at Imperial led by Professor Magdi Yacoub showed that resting the heart using an LVAD fitted for a limited time can help the heart muscle to recover. The new study is a major step in understanding the mechanisms for this improvement at the level of heart muscle cells.
The Imperial researchers studied the changes that occur in heart muscle cells during heart failure in rats, and whether "unloading" the heart can reverse these changes.
"If you injure a muscle in your leg, you rest it and this allows it to recover," said Dr Cesare Terracciano, from the National Heart and Lung Institute (NHLI) at Imperial, who supervised the study. "The heart can't afford to rest -- it has to keep beating continuously. LVADs reduce the load on the heart while maintaining the supply of blood to the body, and this seems to help the heart recover. We wanted to see what unloading does to heart muscle cells, to see how this works."
To study the effect of unloading, they transplanted a failing heart from one rat into another rat alongside that rat's healthy heart, so that it received blood but did not have to pump. After the heart was able to rest, several changes in the structure of heart muscle cells that impair how well they can contract were reversed.
"This is the first demonstration that this important form of remodelling of heart muscle cells induced by heart failure is reversible," said Michael Ibrahim, also from the NHLI at Imperial, who conducted the research for his PhD funded by the British Heart Foundation. "If we can discover the molecular mechanisms for these changes, it might be possible to induce recovery without a serious procedure like having an LVAD implanted."
The most profound cellular effects observed in this study concerned structures called t-tubules. These allow electrical signals to travel deep into the muscle cells so that all of the fibres contract simultaneously. T-tubules are densely packed and regular in healthy heart cells, enabling efficient muscle contraction, but they become sparse and irregular after heart failure. Unloading the heart led to the t-tubules returning to normal.

**Source: Imperial College London

Rare immune cells could hold key to treating immune disorders

The characterisation of a rare immune cell's involvement in antibody production and ability to 'remember' infectious agents could help to improve vaccination and lead to new treatments for immune disorders, say researchers from the Walter and Eliza Hall Institute. The cells, called T follicular helper cells, represent less than half of one per cent of all immune cells, but play a critical role in antibody production and developing long-lasting immunity. However, the cells are also dramatically increased in chronic inflammatory disease, suggesting that they could be a therapeutic target for treating these diseases.
The research team, led by Dr Katja Lüthje and Associate Professor David Tarlinton, from the institute's Immunology division, and Dr Stephen Nutt from the institute's Molecular Immunology division, discovered a means of identifying the rare T follicular helper cells while they are actually involved in instructing the immune response, revealing for the first time the possible fates of these cells. The research was recently published in the journal Nature Immunology.
Dr Lüthje said the research team discovered T follicular helper cells were essential for developing strong and specific antibody responses to infectious agents. "Antibodies are fundamental to the body's defence against infection," Dr Lüthje said. "Antibody production critically relies on the interaction of two cell types: B cells that produce antibody, and helper T cells that recruit and 'teach' the B cells how to respond to infectious agents. In this study, we used a special fluorescent protein to help identify exactly which cells were involved in the process, and discovered that, amongst the rare T follicular helper cells, only a subset were actively involved in instructing B cells in antibody production."
Dr Nutt said that one of the key findings made by the research team was that T follicular helper cells can remember being exposed to infectious agents, allowing them to rapidly react to subsequent attacks. "The success of vaccines relies on antibody production and long-term immune 'memory'; without these, most routinely-used vaccines, including measles, mumps and tetanus, do not work," Dr Nutt said. "It is well established that antibody-producing B cells can remember a particular infectious agent and rapidly respond if and when they come across it again. Our study shows, for the first time, that T follicular helper cells also develop memory to rapidly respond to infection."
"This finding is incredibly important for the development of vaccines, which relies on immune memory to prevent subsequent infections," Dr Nutt said. "Some vaccines, such as polio are very effective at establishing long-term immunity, while others, such as the cholera vaccine are not particularly effective and need ongoing boosters. It may be that the vaccines are not establishing good T follicular helper cell memory, and this could be something to look at for developing new vaccines for diseases that currently do not have good preventive treatments."

**Source: Walter and Eliza Hall Institute