Curry spice component may help slow prostate tumor growth

Curcumin, an active component of the Indian curry spice turmeric, may help slow down tumor growth in castration-resistant prostate cancer patients on androgen deprivation therapy (ADT), a study from researchers at Jefferson's Kimmel Cancer Center suggests. Reporting in a recent issue of Cancer Research, Karen Knudsen, Ph.D., a Professor of Cancer Biology, Urology and Radiation Oncology at Thomas Jefferson University, and colleagues observed in a pre-clinical study that curcumin suppresses two known nuclear receptor activators, p300 and CPB (or CREB1-binding protein), which have been shown to work against ADT.
ADT aims to inhibit the androgen receptor -- an important male hormone in the development and progression of prostate cancer -- in patients. But a major mechanism of therapeutic failure and progression to advanced disease is inappropriate reactivation of this receptor. Sophisticated tumor cells, with the help of p300 and CPB, sometimes bypass the therapy.
Thus, development of novel targets that act in concert with the therapy would be of benefit to patients with castration-resistant prostate cancer.
For the study, prostate cancer cells were subjected to hormone deprivation in the presence and absence of curcumin with "physiologically attainable' doses. (Previous studies, which found similar results, included doses that were not realistic.)
Curcumin augments the results of ADT, and reduced cell number compared to ADT alone, the researchers found. Moreover, the spice was found to be a potent inhibitor of both cell cycle and survival in prostate cancer cells.
To help support their findings, the researchers also investigated curcumin in mice, which were castrated to mimic ADT. They were randomized into two cohorts: curcumin and control. Tumor growth and mass were significantly reduced in the mice with curcumin, the researchers report.
These data demonstrate for the first time that curcumin not only hampers the transition of ADT-sensitive disease to castration-resistance, but is also effective in blocking the growth of established castrate-resistant prostate tumors.
"This study sets the stage for further development of curcumin as a novel agent to target androgen receptor signaling," said Dr. Knudsen. "It also has implications beyond prostate cancer since p300 and CBP are important in other malignancies, like breast cancer. In tumors where these play an important function, curcumin may prove to be a promising therapeutic agent."

**Source: Thomas Jefferson University

Arthritic knees, but not hips, have robust repair response

Researchers at Duke University Medical Center used new tools they developed to analyze knees and hips and discovered that osteoarthritic knee joints are in a constant state of repair, while hip joints are not. "This suggests the knee has capacity for repair we didn't know about and the main treatment strategy probably would need to focus on turning off the breakdown of knee tissue," said Virginia Kraus, MD, PhD, professor of Rheumatology and Immunology at Duke. "I was hugely surprised to find this."
This suggests that knee and hip osteoarthritis may need different treatment approaches, Kraus said.
Perhaps the natural repair response would be sufficient to lead to a reversal or halting of the disease process in the knee if the joint breakdown could be halted, Kraus said.
"At least with the knee you've got an ongoing repair response that we didn't appreciate until now," Kraus said. "If you could capitalize on that and turn off the degradative (breakdown) processing you might have some good effects."
The findings, published in the Journal of Biological Chemistry on Feb. 10, suggest that for hips, however, halting the degenerative process might not be enough. The hips would need a treatment to both stop degeneration as well as stimulate factors that could help to begin repair.
The knee is very accessible for injections, so it would make sense to inject the knee with agents that could turn off the degradative processes, and these could be delivered periodically with close monitoring, Kraus said. "That seems like a very viable strategy."
A number of treatment strategies are being tested in clinical trials to switch off the joint breakdown processes, and Kraus is hopeful that this approach will lead to treatment breakthroughs for osteoarthritis.
A cocktail of drugs might be needed for the hip, however, both to halt the degradation and to stimulate the right type of reparative elements.
"I am speculating that a single agent would work for the knee," Kraus said.
The findings about the knee were shocking to her, because the literature for years had compared the knee and ankle. Scientists knew the ankle was resistant to osteoarthritis, but the knee was very susceptible.
The thinking was that the ankle joint bones fit together well, like a ball in a socket, so the joint cartilage is less likely to degrade, while the knee joint bones fit less well together and require tissue, like the meniscus, to create a better fit -- so knee cartilage is more likely to degrade.
"What we found is startling, because the hip joint also has a ball-in-socket structure yet it degrades and fails to mount a strong repair response," Kraus said. "We think this means that joint congruency alone cannot explain the difference in the repair response of joints, so there is more to learn."
Kraus and her team discovered a biomarker that is a measure of an altered (deaminated) protein, called D-COMP. In the circulation it signals hip degeneration and in cartilage it provides insight into the repair response of joint tissues. Kraus said this is the first biomarker specific to a particular joint site, and may be developed into a monitoring tool for hip-joint breakdown.
The next step is to understand the reasons for the difference between knees and hips and also to use the new tools to analyze the ankle for its level of repair response.
"Why is the ankle less susceptible than the knee to osteoarthritis?" Kraus asked. "Can we develop other tools to be specific indicators of joint health for other joints in the body?"

**Source: Duke University Medical Center

La ESA ensaya un sistema 3D para cuidar la salud de los astronautas

Un sistema basado en la realidad aumentada, difundido por la Agencia Espacial Europea (ESA), ayudará a los astronautas a cuidar de su salud en el espacio y les permitirá realizar intervenciones quirúrgicas de forma autónoma.
El proyecto, que se encuentra en fase de prototipo y ha sido impulsado por dos centros de investigación alemanes y un consorcio de aplicaciones espaciales con sede en Bélgica, lleva el nombre de Sistema de Diagnosis Médica y Cirugía Asistida por Ordenador (CAMDASS).
El dispositivo requiere primero registrar el cuerpo del paciente con una cámara tras haberle colocado unas marcas de referencia, y luego superpone sobre el campo de visión del usuario unos gráficos en tres dimensiones generados por ordenador que proporcionan información en tiempo real sobre lo que tiene ante sí y cómo actuar.
Esta técnica de visualización se ha comenzado a experimentar con los exámenes por ultrasonidos, porque la ESA dispone ya de los equipos necesarios para realizarlos, pero es una tecnología que según la agencia podría aplicarse a cualquier procedimiento médico.

-Ensayos en un hospital
Los ensayos realizados en un hospital en Bruselas demostraron que usuarios sin experiencia pudieron llevar a cabo procedimientos relativamente difíciles gracias a las indicaciones del CAMDASS.
El dispositivo muestra a los usuarios cómo colocar y mover de forma adecuada el transductor de ultrasonidos para examinar el área de interés, y presenta además una serie de imágenes con indicaciones sobre lo que se pueden encontrar.
Con este avance, según indicó la ESA, se pretende conseguir que los astronautas puedan solucionar los problemas médicos por su cuenta, porque a medida que se alejen más de la Tierra en futuras misiones del Sistema Solar se incrementa la posibilidad de que haya interferencias en las comunicaciones con la base.
Pero el CAMDASS, añadió la ESA, también podría utilizarse como un sistema de "telemedicina por vía satélite", para "prestar primeros auxilios en países en vías de desarrollo o en la Antártida", o igualmente como herramienta para prestar primeros auxilios.

*AGENCIAS

Starve a virus, feed a cure?

A protein that protects some of our immune cells from the most common and virulent form of HIV works by starving the virus of the molecular building blocks that it needs to replicate, according to research published online in Nature Immunology. The finding comes from an international team of researchers including scientists from the University of Rochester Medical Center, NYU Langone Medical Center, several institutions in France -- and a graduate student who who is a political refugee from Africa and is now at work in a Rochester laboratory, intent on helping his people who have been devastated by the HIV epidemic.
While researchers hope the work will one day lead to a way to make anti-HIV drugs more effective by increasing their potency against the virus, they're also excited about its implications for our knowledge of other pathogens, such as herpes viruses, which use the same machinery within our cells that HIV does to replicate.
"The findings may explain why certain anti-HIV drugs used today are more effective under some circumstances and not others," said Baek Kim, Ph.D., professor of Microbiology and Immunology at the University of Rochester Medical Center and one of three corresponding authors of the paper. "It also provides new insights on how many other viruses that afflict people operate in the body."
The work centers on a protein known as SAMHD1, which is found in white blood cells known as macrophages and related cells known as dendritic cells. Last year scientists discovered that the molecule makes it difficult for HIV-1 to infect macrophages -- cells that specialize in gobbling up and destroying invaders like viruses.
Now researchers have discovered that the molecule cuts off the supply line of the raw material that HIV needs to create DNA and replicate. That raw material, dNTP, comprises the building blocks of DNA, and without it, HIV can't recreate its DNA in our cells.
The team found that SAMHD1 destroys most of these building blocks, making it nearly impossible for HIV-1 to replicate itself where SAMHD1 resides -- the macrophages. Instead, HIV-1 uses the macrophage as a safe haven, surviving in patients for years as it dodges the immune system as well as the drugs designed to kill it. It's thanks largely to its ability to hide out in the body that HIV is able to survive for decades and ultimately win out against the body's relentless immune assault.
The team also discovered how a protein in the other common type of HIV -- HIV-2, which is found mainly in Africa -- knocks out SAMHD1. They found that the protein Vpx destroys SAMHD1, clearing the way for HIV-2 to infect macrophages. While scientists have known that HIV-2 needs Vpx to infect macrophages, they hadn't known precisely why.
Interestingly, while one might think that a virus that is able to replicate itself in crucial cells like macrophages might be more dangerous than one that cannot, that's not the case with HIV. HIV-2 is actually less virulent than HIV-1.
"We don't know precisely how SAMHD1 and Vpx affect the virulence of HIV-1 and HIV-2, but it's something we're actively exploring," said Kim. "In this case, the ability of HIV-2 to replicate more quickly in macrophages does not help it become more virulent."
One possibility is that, like a starving man who becomes more and more desperate for food, the virus -- when faced with a shortage of raw materials -- puts its mutation gear into overdrive, creating more mutations in an effort to circumvent the pathway blocked by SAMHD1. Such constant mutations are one feature of HIV that makes it so challenging to treat patients.
"It makes sense that a mechanism like this is active in macrophages," said Kim. "Macrophages literally eat up dangerous organisms, and you don't want those organisms to have available the cellular machinery needed to replicate. And macrophages themselves don't need it, because they don't replicate. So macrophages have SAMHD1 to get rid of the raw material those organisms need to copy themselves. It's a great host defense.
"The work suggests new ways to target virus replication in macrophages, a critically important cell population that serves as a key reservoir of virus infection and a contributor to HIV-induced disease," added Kim.
At Rochester, Kim was joined in the research by graduate student Waaqo Daddacha, one of two first authors of the paper. A native of the Oromia region of Ethiopia, Daddacha came as a political refugee to the United States. He started out as a computer programmer, then decided to pursue HIV research as a way to help his homeland, where the rate of HIV is one of the highest in the world. As an undergraduate in Minnesota, he visited several laboratories around the nation that focus on HIV, eventually settling on the Kim lab, which he joined four years ago.
"Back home, many people are infected with HIV, and many people are dying because of it. I wanted to contribute to help solve the problem, and that's why I decided to pursue HIV research," said Daddacha, who still has family in Oromia. In Kim's lab he is focusing on understanding drug resistance among HIV patients and on finding ways to limit resistance to make the drugs more effective in patients.

**Source: University of Rochester Medical Center

Researchers discover molecular secrets of ancient Chinese herbal remedy

For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, a compound derived from this extract's bioactive ingredient, could be used to treat many autoimmune disorders as well. Now, researchers from the Harvard School of Dental Medicine have discovered the molecular secrets behind this herbal extract's power. It turns out that halofuginone (HF) triggers a stress-response pathway that blocks the development of a harmful class of immune cells, called Th17 cells, which have been implicated in many autoimmune disorders.
"HF prevents the autoimmune response without dampening immunity altogether," said Malcolm Whitman, a professor of developmental biology at Harvard School of Dental Medicine and senior author on the new study. "This compound could inspire novel therapeutic approaches to a variety of autoimmune disorders."
"This study is an exciting example of how solving the molecular mechanism of traditional herbal medicine can lead both to new insights into physiological regulation and to novel approaches to the treatment of disease," said Tracy Keller, an instructor in Whitman's lab and the first author on the paper.
This study, which involved an interdisciplinary team of researchers at Massachusetts General Hospital and elsewhere, will be published online February 12 in Nature Chemical Biology.
Prior research had shown that HF reduced scarring in tissue, scleroderma (a tightening of the skin), multiple sclerosis, scar formation and even cancer progression. "We thought HF must work on a signaling pathway that had many downstream effects," said Keller.
In 2009, Keller and colleagues reported that HF protects against harmful Th17 immune cells without affecting other beneficial immune cells. Recognized only since 2006, Th17 cells are "bad actors," implicated in many autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis and psoriasis. The researchers found that minute doses of HF reduced multiple sclerosis in a mouse model. As such, it was one of a new arsenal of drugs that selectively inhibits autoimmune pathology without suppressing the immune system globally. Further analysis showed that HF was somehow turning on genes involved in a newly discovered pathway called the amino acid response pathway, or AAR.
Scientists have only recently appreciated the role of the nutrient sensing-AAR pathway in immune regulation and metabolic signaling. There is also evidence that it extends lifespan and delays age-related inflammatory diseases in animal studies on caloric restriction. A conservationist of sorts, AAR lets cells know when they need to preserve resources. For example, when a cell senses a limited supply of amino acids for building proteins, AAR will block signals that promote inflammation because inflamed tissues require lots of protein.
"Think about how during a power outage we conserve what little juice we have left on our devices, foregoing chats in favor of emergency calls," said Whitman. "Cells use similar logic."
For the current study, the researchers investigated how HF activates the AAR pathway, looking at the most basic process that cells use to translate a gene's DNA code into the amino acid chain that makes up a protein.
The researchers were able to home in on a single amino acid, called proline, and discovered that HF targeted and inhibited a particular enzyme (tRNA synthetase EPRS) responsible for incorporating proline into proteins that normally contain it. When this occurred, the AAR response kicked in and produced the therapeutic effects of HF-treatment.
Providing supplemental proline reversed the effects of HF on Th17 cell differentiation, while adding back other amino acids did not, establishing the specificity of HF for proline incorporation. Added proline also reversed other therapeutic effects of HF, inhibiting its effectiveness against the malaria parasite as well as certain cellular processes linked to tissue scarring. Again, supplementation with other amino acids had no such effect. Such mounting evidence clearly demonstrated that HF acts specifically to restrict proline.
The researchers think that HF treatment mimics cellular proline deprivation, which activates the AAR response and subsequently impacts immune regulation. Researchers do not yet fully understand the role that amino acid limitation plays in disease response or why restricting proline inhibits Th17 cell production.
Nevertheless, "AAR pathway is clearly an interesting drug target, and halofuginone, in addition to its potential therapeutic uses, is a powerful tool for studying the AAR pathway," said Whitman.

*Source: Harvard Medical School

Aumentan los casos de ansiedad, que afectan el doble a las mujeres

La mujer tiene dos veces más riesgo que el hombre de padecer trastornos de ansiedad, una patología que está creciendo significativamente en la última década, según los especialistas que participan en el VI Congreso Nacional de Ansiedad y Trastornos Comórbidos celebrado en Barcelona.
Según los organizadores del congreso, «la prevalencia de los trastornos de ansiedad ha presentado un significativo aumento en las últimas décadas en el mundo occidental».

-Diagnóstico
Las causas de este aumento, según los especialistas, son múltiples, aunque señalan que algunas podrían ser el crecimiento de las expectativas de vida, un diagnóstico más precoz o la irrupción de nuevas patologías emergentes.
Los psiquiatras, que también ven en la situación de crisis un factor que predispone a padecer ansiedad, consideran que mantener un cierto nivel de ansiedad en circunstancias cotidianas «no solo es bueno, sino que permite una mejor adaptación e incluso ha ayudado a la supervivencia de la especie».

La OMC diseña un Plan Estratégico para mejorar la cumplimentación de los Certificados Médicos de Defunción

La Organización Médica Colegial (OMC) ha puesto en marcha un plan estratégico dirigido a todos los profesionales médicos y a las instituciones en donde ejercen, con el fin de mejorar la cumplimentación de los Certificados Médicos de Defunción.
Para ello una Comisión formada por los responsables de las Vocalías Nacionales del Consejo General de Colegios de Médicos, de las Áreas de Comunicación, Jurídica y Tecnológica de la OMC, de la Fundación para la Formación de la OMC así como miembros de la Permanente se han reunido para planificar esta estrategia que se desarrollará a lo largo del año 2012 y 2013.
La primera actividad a realizar será una Jornada sobre Certificación Médica de Defunción que se llevará a cabo el próximo día 1 de Marzo en la sede de la Organización Médica Colegial.
Igualmente entre las acciones que se han acordado llevar a cabo, está la de realizar un Curso de Formación de Formadores dirigidos a responsables de las vocalías de todos los colegios de médicos en la que están representados médicos de atención primaria, de hospitales, en formación, de ejercicio libre y especialistas entre otros de medicina legal y forense, con la finalidad de que estos trasladen a su vez a todos los colegiados la información y formación necesaria para la mejor cumplimentación de los certificados médicos de defunción.
Estas acciones forman parte de un plan de formación que viene realizando la OMC desde que, en 2009 se reformó el actual modelo de Certificado Médico de Defunción que sirve para realizar la inscripción del fallecimiento en el Registro Civil y también para elaborar las estadísticas del Instituto Nacional de Estadística sobre las causas de la muerte. Esta unificación en un documento único fue posible gracias al consenso entre los Ministerios de Justicia y Sanidad, el Instituto Nacional de Estadística y la OMC.
El Certificado Médico de Defunción es un documento jurídico-administrativo necesario para la inscripción en el Registro Civil del fallecido y obtener licencia de enterramiento en el caso de muerte natural. La OMC es el único organismo autorizado a editar y distribuir los impresos de los certificados médicos oficiales, entre ellos, el certificado médico de defunción.
La OMC quiere, con estas iniciativas, responder en la mejora de la calidad asistencial y al deber legal del médico que haya asistido al difunto en su enfermedad o que haya tenido que reconocer el cadáver, de certificar su muerte, algo que también se reconoce en el nuevo Código de Deontología Médica que dice en su Artículo 36.6: “aunque el médico que haya tenido la mayor carga asistencial sobre el paciente es el que tiene la mayor responsabilidad ética de cumplimentar el certificado de defunción en todos sus apartados, no es deontológicamente aceptable rehuir el compromiso de certificarla cuando se produce si se ha presenciado la misma, se conoce al paciente o se tiene a disposición la historia clínica”.
Además de las iniciativas formativas, la OMC está adherida al programa Certifica, del Ministerio de Sanidad, Servicios Sociales e Igualdad, un proyecto de autoformación médica a través de Internet, de gran ayuda para cumplimentar correctamente en este modelo de Certificado. A este programa está también adherido el INE y consejerías de sanidad de diversas comunidades autónomas.
Este programa cuenta con un decálogo que incluye una serie de recomendaciones, entre ellas, la descripción de la secuencia lógica de las patologías y la de hacer constar una única causa de muerte fundamental que, según el criterio del médico certificador es la desencadenante de todo el proceso que ha llevado a la defunción. Y explica que, en los casos de que el paciente tenga varias enfermedades, debe ser el criterio del médico el que dictamine de entre todas, aquellas que con mayor probabilidad pudo ser la que desencadenó el proceso y fue la causa fundamental de la muerte.
El programa Certifica ofrece también información jurídico legal sobre diversos temas, entre ellos, la relacionada con nacimientos, abortos y autopsias, así como 180 casos prácticos de gran utilidad para la formación de los médicos.
Finalmente, comentar que esta Estrategia de mejora de la Certificación Médica de la Defunción se realiza en colaboración con el Instituto Nacional de Estadística y contará con el apoyo del Ministerio de Sanidad, Servicios Sociales e Igualdad.

**Publicado en "MEDICOS Y PACIENTES"