Genetic study sheds new light on auto-immune arthritis

The team of researchers from the Universities of Bristol, Queensland (Australia), Oxford, Texas and Toronto, used a technique called genome-wide association where millions of genetic markers are measured in thousands of people that have the disease and thousands of healthy individuals. Markers which are more frequent in individuals with the disease are more likely to be involved in the condition.
Using this approach the investigators found an additional seven genes likely to be involved in the condition, bringing the total number of genes known to predispose to AS to thirteen. Many of the new genes are already known to be involved in inflammatory and immune processes, providing researchers with further clues about how the disease arises. Two of the new genes are also known to predispose to other auto-immune conditions including Crohn's disease (a form of inflammatory bowel disease) and Celiac disease (an auto-immune intestinal disease).
Researchers were also able to demonstrate an interaction between a genetic mutation called HLA-B27 and a mutation in a gene called ERAP1. Specifically, the ERAP1 mutation only predisposed to disease in those individuals who tested positive for the HLA-B27 mutation.
Dr David Evans from the University of Bristol said: "This finding is important in a number of ways. First of all it's one of the first convincing examples we have of one mutation influencing the effect of another mutation in the development of a relatively common disease. This is exciting because it implies that there may be other examples of this phenomenon in other common diseases that we don't know about yet.
"Second, the interaction itself tells us something very fundamental about how AS is caused. Prior to this study there were a number of competing theories about how the disease was caused. Our study suggests very strongly which one of these competing hypotheses is likely to be correct."
Finally, the researchers also identified a single genetic marker which could be used to assist in diagnosis of Ankylosing Spondylitis.
"AS is notoriously difficult to diagnose in its early stages which can lead to costly delays in its treatment," said Dr Evans. "Typically diagnosis consists of a combination of X-rays, patient symptoms and expensive immunological assays in the laboratory. This genetic marker could easily take the place of an expensive immunological assay. What would normally cost £40-£50 could be done easily for a fraction of the price."

*Source: University of Bristol

New genetic clues for schizophrenia

De novo mutations – genetic errors that are present in patients but not in their parents – are more frequent in schizophrenic patients than in normal individuals, according to an international group of scientists led by Dr. Guy A. Rouleau of the University of Montreal and CHU Sainte-Justine Hospital. The discovery, published today in Nature Genetics, may enable researchers to define how the disease results from these mutations and eventually develop new treatments for it. "The occurrence of de novo mutations, as observed in this study, may in part explain the high worldwide incidence of schizophrenia," says Dr. Rouleau, who is also Director of the CHU Sainte-Justine Research Center and researcher at the University of Montreal Hospital Research Centre. "Because the mutations are located in many different genes, we can now start to establish genetic networks that would define how these gene mutations predispose to schizophrenia," adds Simon Girard, the student who performed the key experiments that led to this discovery. "Most of the genes identified in this study have not been previously linked to schizophrenia, thereby providing new potential therapeutic targets."
Schizophrenia is a major mental disorder characterized by a wide spectrum of symptoms, including delusions, hallucinations, disturbances in thinking, and deterioration of social behaviours. According to the World Health Organization, as many as 24 million individuals worldwide suffer from schizophrenia and over half of them are not receiving appropriate care to relieve their symptoms.
Dr. Rouleau's team used modern DNA sequencing technologies to identify genetic changes in patients with schizophrenia whose parents showed no signs of the disease. To identify genetic mutations associated with schizophrenia, Dr. Rouleau and his team analysed approximately 20,000 genes from each participant in the study. The research team was especially interested in "de novo" mutations, meaning those that are present in patients but absent in their parents.
"Our results not only open the door to a better understanding of schizophrenia," adds Dr. Rouleau. "They also give us valuable information about the molecular mechanisms involved in human brain development and function."
The identification of de novo mutations in schizophrenia supports the hypothesis proposed by Dr. Rouleau in 2006, that this type of mutation plays a role in several diseases affecting brain development such as autism, schizophrenia and mental retardation.

**Source: University of Montreal

Según un estudio, hombre obeso=esperma débil

El esperma de los hombres obesos es más pobre, lo que influye en sus posibilidades de tener descencencia. Así lo refleja un estudio francés, presentado en el seno del Congreso de la Sociedad Europea de Reproducción Humana, que se ha celebrado estos días en Estocolmo (Suecia). La investigación, dirigida por Paul Cohen-Bacrie, del grupo de laboratorios Unilabs, incluyó a 1.940 varones de una docena de países. El equipo analizó parámetros como el PH, la movilidad de los gametos, la concentración o la morfología. En los hombres con sobrepeso (índice de masa corporal de entre 25 y 30) u obesidad (superior a 30), la concentración de espermatozoides en el semen era un 10 y un 20 por ciento más bajos respecto a los parámetros estándar. En el caso de los que acumulaban más kilos, la movilidad de los gametos también estaba reducida. En cuanto al recuento total de espermatozoides, mientras que en personas que están en un peso normal ronda los 184 a 194 millones por mililitro en el varón con sobrepeso es de 164/186 y en los obesos 135/157 millones.
Por otra parte, los fármacos empleados en la fecundación «in vitro» para mujeres mayores podrían incrementar su riesgo de tener un bebé con Síndrome de Down, según un estudio realizado por el London Bridge Fertility, Gynaecology and Genetics Centre (Reino Unido). Cuando los autores de este trabajo estudiaron estos óvulos ya fertilizados, vieron que algunos presentaban errores genéticos. Este tipo de fallos podían hacer que el embarazo fracasara o hacer que el bebé naciera con alguna enfermedad genética. Un análisis detallado de 100 de los óvulos defectuosos reveló que muchos de los errores estaban relacionados con una duplicación del material genético en espiral, conocido como cromosomas. A menudo, los errores generaban una copia extra del cromosoma 21, circunstancia que genera la aparición del síndrome de Down. Otro estudio invita a que las mujeres que deseen quedarse embarazadas deben cepillarse correctamente los dientes y usar hilo dental de forma habitual para evitar la gingivitis, una enfermedad de las encías y que afecta las posibilidades de concepción. En concreto, la enfermedad periodontal puede retrasar el tiempo que se tarda en concebir un hijo una media de dos meses. Según los investigadores, el culpable de este hecho corresponde a la inflamación causada por las bacterias orales que pueden tener un efecto en cadena sobre el tejido en el sistema reproductivo. Ésta es la primera vez que se ha identificado esta patología entre los factores que influyen en la posibilidad de concebir un hijo.

**Publicado en "LA RAZON"

La tanorexia, una enfermedad más que seria

Su objetivo es lograr un moreno permanente, un bronceado eterno. Y ni los más de 35 grados a la sombra, ni el sudor recorriendo su cuerpo... Ni siquiera el tono rojizo de la piel quemada son suficientes para alejarles de los rayos. Son adictos al sol, lo que ya definen como tanoréxicos (del término «bronceado», en inglés «tan»). Aunque la comunidad médica todavía no se ha hecho demasiado eco sobre este concepto, algunos expertos explican que, entre sus síntomas se observa una obsesión por estar más morenos que los demás que, a su vez, genera ansiedad debido a que se está en continua competición con quienes les rodean y se frustra cuando no lo logra. Y cuando la obsesión da un giro hasta alcanzar un estado crítico, el paciente puede sufrir un trastorno dismórfico corporal.

Julián Conejo-Mir, jefe de Servicio del Hospital Virgen del Rocío de Sevilla y presidente de Honor de la Academia Española de Dermatología y Venerología (AEDV) explica que «es un trastorno dismórfico corporal, incluido en el término dismorfobia, que incluye otros como la anorexia, la vigorexia, etc. Lo pusieron de moda los Beckham. Ahora está también el diseñador Valentino o la actriz Lindsay Lohan».

Las generaciones que hoy pasan de los 50 se echan las manos a la cabeza al pensar en lo que en su día hicieron para lograr esa tonalidad, pero los jóvenes no son conscientes de lo que la mercromina mezclada con la crema o las cabinas bronceadoras pueden hacer en su piel a largo plazo. Según Carolyn Heckman, investigadora del Centro Oncológico Fox Chase de Philadelphia (Estados Unidos) «quienes tienen más riesgo de caer en esta dependencia son las jóvenes de piel blanca y habituales usuarias de estas cabinas. A este perfil le suelen acompañar otros problemas psicológicos como ansiedad, cambios de humor y empleo de otro tipo de sustancias».

Por su parte, Lidia Trasobares, responsable de la Consulta de Melanoma del Servicio de Dermatología del Hospital Universitario Príncipe de Asturias de Madrid, enfatiza que «tuve en consulta una paciente con riesgo de sufrir un tumor de piel que aseguraba que no iba a dejar de tomar el sol porque se iba a deprimir, que prefería morirse que dejar de estar morena». Gema cumple el perfil. Solía hacer submarinismo y pasaba días en la playa. Pero la protección y el sentido del peligro fueron desterrados por el «ansia» del bronceado. «Como soy morena, nunca me he echado crema». Y la amenaza del sol terminó por cumplirse. «Un fin de semana me abrasé. Desperté con la cara hinchada y me pelé. Ahora tengo más arrugas, la cara muy seca, y me molesta el sol, me salen manchas».

Pero, de las torturas a las que se somete el cuerpo, la última y más peligrosa es inyectarse Melotan, un producto que, pese a estar aún en fase de experimentación, se vende de forma fraudulenta por internet. «Es un análogo de la melanocortina que broncea, aumenta la potencia sexual y reduce el apetito. Induce la producción de melanina», dice Luis Hueso, dermatólogo del Hospital de Manises de Valencia. Fue en este centro donde hicieron un estudio tras recibir un paciente que se inyectó la sustancia y sufrió la aparición de nevus atípicos en su cuerpo de forma brusca. El fármaco estaría pensado para «prevenir dolencias dermatológicas, como dermatosis fotoinducidas que se pueden activar con la exposición solar», dice Hueso. «También para broncearse, sin necesidad de tomar el sol».

Entre las consecuencias que ya se barajan, se encuentra la posibilidad de producir cáncer. No obstante, los expertos se muestran precavidos «porque se está diciendo que produce melanoma y no tenemos evidencia científica de ello, pero sí de multiplicación y transformación de nevus. El estudio demostró lunares con potencial riesgo de transformación maligna. Pero no ha desarrollado ningún melanoma», aclara el miembro de la AEDV. Además, existen casos publicados en la literatura científica internacional semejantes al nuestro, con multiplicación y transformación de nevus en pacientes que habían utilizado Melanotan. En uno de ellos, sí que se ha documentado la aparición de un melanoma», concluye. Edermatólogo concluye que el medicamento «puede producir hipertensión arterial, algo que no se ha advertido hasta el momento».

**Publicado en "LA RAZON"

Experiment aboard shuttle Atlantis will test novel therapy to build bone during space travel

Astronauts lose a significant amount of bone mass during space travel and with long duration flights there is concern that this bone loss could lead to an increased risk of fractures. When the final mission of NASA's 30-year Space Shuttle program is launched on July 8, an animal experiment to test a novel therapy to increase bone mass will be on board. Led by a consortium of scientists from Beth Israel Deaconess Medical Center (BIDMC), Amgen, Inc., UCB, BioServe Space Technologies and the University of North Carolina, and funded by NASA's Ames Research Center, the research will not only address a serious problem that affects astronauts who spend weeks and months in a low-gravity environment, but may also yield novel insights into the prevention and treatment of skeletal fragility among patients on earth who are less active due to aging or illness.
"Mechanical loading is required to maintain musculoskeletal health," explains Co-Principal Investigator Mary Bouxsein, PhD, a scientist in BIDMC's Center for Advanced Orthopaedic Studies and Assistant Professor of Orthopaedic Surgery at Harvard Medical School.
"On earth, our bones experience mechanical forces from being pushed and pulled by muscles that work against gravity to keep us upright and moving around, as well as from the impact of our body weight against the ground," she explains. "These forces are much lower in micro-gravity environments and, as a result, the rate of bone loss among astronauts is about 10 times greater than that seen in postmenopausal women. So, while this research is designed to better understand and prevent skeletal fragility among astronauts, it may also tell us a great deal about the future potential of this novel therapy to improve bone strength here on earth, in both older persons and in individuals with reduced physical activity due to various clinical conditions, such as stroke, spinal cord injury or cerebral palsy."
NASA's Commercial Biomedical Test Module (CBTM-3) experiment will examine whether the use of an antibody that blocks the action of the protein sclerostin can lead to gains in bone mass and thereby prevent skeletal deterioration. (The sclerostin molecule is a potent inhibitor of bone formation that is produced by osteocytes, bone cells which form a "nerve-like" network that enable the skeleton to "feel" and respond to mechanical strain.)
"This proof-of-principle study will enhance our understanding of the science behind the sclerostin antibody and arm us with important research to support potential future therapeutic applications in both astronauts and patients suffering from bone loss," notes Amgen Scientific Executive Director Chris Paszty, PhD.
Thirty mice will be flown in space, with half of the animals given a preflight injection of the sclerostin antibody and the remaining mice receiving a placebo. After the flight lands (following 12 days in space), various aspects of the structure, composition, strength and cell and molecular nature of the bones from the flight and ground-based control mice will be analyzed.
"When the mice come back from space, we hope to learn what the effects of microgravity are on the skeleton and on the muscle," explains Bouxsein. "We also want to find out if this new type of therapy will be able to counteract those profound effects and actually promote bone gain in a microgravity environment.
"One in two women and one in five men over age 50 will suffer a fracture resulting from osteoporosis [and bone loss] during their remaining lifetime," she adds. "These fractures have profound personal and societal consequences. With the increasing age of the population there is urgent need to develop bone-building therapies to prevent this type of potentially debilitating injury."

**Source: Beth Israel Deaconess Medical Center

Indoor air pollution linked to cardiovascular risk

An estimated two billion people in the developing world heat and cook with a biomass fuel such as wood, but the practice exposes people – especially women – to large doses of small-particle air pollution, which can cause premature death and lung disease. In a study just published online in the peer-reviewed journal Environmental Health Perspectives, researchers at the University of Wisconsin-Madison have associated indoor air pollution with increased blood pressure among older women.
In a remote area of Yunnan Province, China, 280 women in an ethnic minority called the Naxi wore a portable device that sampled the air they were breathing for 24 hours. The Naxi live in compounds including a central, free-standing kitchen that often has both a stove and a fire pit, says Jill Baumgartner, who performed the study with National Science Foundation funding while a Ph.D. student at UW-Madison.
"I spent a lot of time watching women cook in these unvented kitchens, and within seconds, my eyes would burn, it would get a little difficult to breathe. The women talk about these same discomforts, but they are viewed as just another hardship of rural life," Baumgartner says.
Most women are exposed to this smoke for several hours a day, and even if the cookstove is vented, a second fire is often burning for heat, says Baumgartner, who is now a global renewable energy leadership fellow at the Institute on the Environment at the University of Minnesota.
By correlating exposure over 24 hours with blood pressure, Baumgartner and colleagues associated higher levels of indoor air pollution with a significantly higher blood pressure among women aged 50 and over. Small-particle pollution raises blood pressure over the short term by stimulating the nervous system to constrict blood vessels. In the long term, the particles can cause oxidative stress, which likewise raises blood pressure.
Other studies have shown that improved stoves or cleaner fuels can cut indoor air pollution by 50 to 75 percent. In the Baumgartner study, that reduction in pollution level was linked to a four-point reduction in systolic blood pressure (the first number in a blood pressure reading). Such a change "may be of little consequence for an individual," says co-author Leonelo Baustista, an associate professor of population health sciences at UW-Madison. "However, changes of this magnitude in a population would have a significant, large impact on the risk of cardiovascular disease in the population."
In fact, the researchers concluded that this reduction would translate into an 18 percent decrease in coronary heart disease and a 22 percent decrease in stroke among Asian women aged 50 to 59. These benefits would save the lives of 230,900 Chinese women each year.
Because biomass fuels are also the primary source of energy for more than 2 billion people globally, cleaner fuels and better stoves would produce even greater cardiovascular benefits worldwide.
"This is the first study that links personal exposure to indoor air pollution to blood pressure changes; considering that a couple of billion people are exposed, this represents an extremely important public health discovery," says co-author Jonathan Patz, director of the UW Global Health Institute.
"We have known for years that unvented cooking indoors causes respiratory damage, but now that we have documented cardiovascular effects as well, the rationale for cleaner stoves and better fuels becomes that much stronger," adds Patz, a professor in the Nelson Institute for Environmental Studies.
Although China had a major program to promote cleaner stoves during the 1980s, indoor air pollution problem remains, Baumgartner says.
"Having a cleaner stove or fuel is important, but in these villages, the piece that is missing is education about the health implications. You can have a great stove, but if it is sitting right next to an open fire, the health benefit is lost," Baumgartner says.

**Source: University of Wisconsin-Madison

Detectan factores que pueden confundir el diagnóstico alérgico

La sensibilización a panalergenos podría ser un factor de confusión en el diagnóstico de alérgicos polisensibilizados al polen, así como un marcador para la alergia alimentaria. Esto aparece recogido en un estudio llevado a cabo por el Departamento de Inmunología y Alergia del Hospital Vírgen de la Macarena de Sevilla y que se ha publicado recientemente en la revista "The Journal of Allergy and Clinical Inmunology". Pese a todo, los responsables del estudio han indicado que son necesarios más ensayos para investugar el papel de estas moléculas más a fondo.