Los casos de SIDA en Barcelona siguen a la baja de forma constante desde 1996. El año pasado se diagnosticaron 99 frente a los 119 del 2009. En el caso de los 371 síndromes de VIH detectados en 2010 que no habían desarrollado la enfermedad lo que más preocupa a la Agencia de Salud Pública de Barcelona es que el 48% de ellos empezaron el tratamiento con retraso. De ahí que se insista una y otra vez en la prevención. Con las estadísticas en la mano, los VIH aumentaron el año pasado un 37% respecto a 2009, un incremento que se asocia al hecho de que desde el año pasado los nuevos diagnósticos VIH deben ser declarados obligatoriamente dentro del registro de enfermedades infecciosas. Hasta ese momento, el paciente decidía si su caso se declaraba o no.
Y otro grupo de enfermedades que están creciendo en los últimos tres años son las infecciones de transmisión sexual, concretamente los infectados por sífilis y gonorrea. Esas enfermedades son de declaración obligatoria desde 2007 y desde 2008 el número de casos detectados se ha ido incrementando. Los infectados de sífilis han pasado, por ejemplo, de 170 en 2008 a 303 el año pasado. De los casos detectados en 2010, el 93% de los pacientes eran hombres y el 82% se declararon homosexuales. “Por eso tenemos que insistir en el uso del preservativo”, ha manifestado el gerente de la ASPB, Conrad Casas.
En 2010, las enfermedades cardiovasculares fueron las principales causas de mortalidad, seguidas de las causas relacionadas con el tabaco en hombres y las enfermedades degenerativas cerebrales en mujeres. De las estadísticas del informe de Salud de la ciudad se desprende que la incidencia de la tuberculosis se está ralentizando progresivamente aunque en el último año haya tenido un repunte. Se trata de una enfermedad ligada a las condiciones de vida desfavorables, de la que en 2010 se registraron 429 casos en residentes en Barcelona, la proporción es de 26,5 casos por 100.000 habitantes. En 2009, la proporción era de 24 casos por cada 100.000 habitantes. Ese repunte es atribuido al empeoramiento de las condiciones de vida por el impacto de la crisis.
El número de suicidios ocurridos en Barcelona en 2008 fue de 32 frente a los 50 de 2009. El incremento se produjo especialmente en mujeres que pasaron de siete en 2008 a 21 el año pasado. El de hombres pasó de 25 a 30. El Ayuntamiento de Barcelona no conoce las cifras de suicidios del año pasado porque los datos se los debe facilitar la Generalitat. El informe también evidencia el incremento de usuarios de la red de servicios de salud mental. En 2010 se atendieron a 36.000 personas adultas y algo más de 7.800 niños y adolescentes, lo que representa un incremento de un 5,2% y un 8%, respectivamente, respecto a 2009. Ese incremento no se asocia a un aumento de los problemas mentales de la población sino a una mayor oferta de servicios y programas, según aclara la Agencia de Salud Pública.
**Publicado en "EL PAIS"
13 December 2011
Gene mutation signals a high risk of recurrence in some older acute-leukemia patients
Older people with acute myeloid leukemia and normal looking chromosomes in their cancer cells have a higher risk of recurrence if they have mutations in a gene called ASXL1, according to a new study by researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James). The study is the first to investigate the influence of these gene mutations on prognosis in patients with cytogenetically normal acute myeloid leukemia (CN-AML), and in conjunction with other prognostic gene mutations. It also reports the first gene-expression signature for CN-AML with mutated ASXL1.
"Our findings could lead to more effective targeted therapies and improved cure rates for these patients," says principal investigator Dr. Clara D. Bloomfield, Distinguished University Professor and Ohio State University Cancer Scholar.
Bloomfield and her colleagues found that patients age 60 and older with CN-AML and ASXL1 mutations had significantly shorter survival than patients with the normal gene -- only 5 percent of patients with the mutation were alive after 3 years, compared to 23 percent of patients without the mutation. Complete remission rates were also significantly lower, at 53 percent for patients with vs. 71 percent for patients without the mutation.
The findings were presented at the 53rd Annual Meeting of the American Society of Hematology. The study's first author, Klaus H. Metzeler, MD, a research fellow at the OSUCCC -- James, also received an "Abstract Achievement Award" in recognition of his novel and clinically relevant work. At the same time, the results were published in the Society's official journal, Blood.
"Mutations in the ASXL1 gene appear to be an important marker of poor prognosis in older AML patients," says Bloomfield, who was also Metzeler's mentor. "Importantly, their negative impact was greatest in patients who, based on established genetic markers, would be expected to have favorable outcomes.
"Mutations in ASXL1 therefore identify a previously unknown high-risk subgroup among older AML patients," Bloomfield notes. "These patients do not do well with our current standard therapy, and therefore might be candidates for treatment with novel drugs in a clinical trial."
The retrospective study involved 423 patients aged 18 to 83 years with CN-AML who were treated on clinical trials.
The researchers focused on patients aged 60 years and older after discovering that ASXL1 mutationswere five times more common in that age group compared with younger patients.
The study also identified the first gene-expression signature associated with this mutated gene in CN-AML, which may provide useful insight into the biology of ASXL1-mutated AML and help design novel treatment approaches for this high-risk group of older patients.
Funding from the National Cancer Institute, the Coleman Leukemia Research Foundation, and the John B. and Jane T. McCoy Chair in Cancer Research supported this research.
**Source: Ohio State University Medical Center
"Our findings could lead to more effective targeted therapies and improved cure rates for these patients," says principal investigator Dr. Clara D. Bloomfield, Distinguished University Professor and Ohio State University Cancer Scholar.
Bloomfield and her colleagues found that patients age 60 and older with CN-AML and ASXL1 mutations had significantly shorter survival than patients with the normal gene -- only 5 percent of patients with the mutation were alive after 3 years, compared to 23 percent of patients without the mutation. Complete remission rates were also significantly lower, at 53 percent for patients with vs. 71 percent for patients without the mutation.
The findings were presented at the 53rd Annual Meeting of the American Society of Hematology. The study's first author, Klaus H. Metzeler, MD, a research fellow at the OSUCCC -- James, also received an "Abstract Achievement Award" in recognition of his novel and clinically relevant work. At the same time, the results were published in the Society's official journal, Blood.
"Mutations in the ASXL1 gene appear to be an important marker of poor prognosis in older AML patients," says Bloomfield, who was also Metzeler's mentor. "Importantly, their negative impact was greatest in patients who, based on established genetic markers, would be expected to have favorable outcomes.
"Mutations in ASXL1 therefore identify a previously unknown high-risk subgroup among older AML patients," Bloomfield notes. "These patients do not do well with our current standard therapy, and therefore might be candidates for treatment with novel drugs in a clinical trial."
The retrospective study involved 423 patients aged 18 to 83 years with CN-AML who were treated on clinical trials.
The researchers focused on patients aged 60 years and older after discovering that ASXL1 mutationswere five times more common in that age group compared with younger patients.
The study also identified the first gene-expression signature associated with this mutated gene in CN-AML, which may provide useful insight into the biology of ASXL1-mutated AML and help design novel treatment approaches for this high-risk group of older patients.
Funding from the National Cancer Institute, the Coleman Leukemia Research Foundation, and the John B. and Jane T. McCoy Chair in Cancer Research supported this research.
**Source: Ohio State University Medical Center
Una terapia génica da buenos resultados con la hemofilia B
La hemofilia B es una enfermedad genética que afecta aproximadamente a uno de cada 30.000 hombres. La causa es un gen defectuoso que impide que fabriquen una proteína (las proteínas son la traducción práctica de las instrucciones codificadas en genes), la llamada factor IX de coagulación. Es por tanto, una de las candidatas ideales para una terapia génica… si esta funciona. Y eso parece que es lo que han conseguido en un reducido ensayo en el que han participado el University College de Londres y el St Jude Children's Research Hospital, un consorcio de EE UU.
En el trabajo, se utilizó un virus de la familia de los adenovirus para introducir una copia buena del gen en los pacientes. Estos microorganismos tienen la propiedad de que integran su ADN en el de las personas que infectan, y, en este caso concreto , se utilizó un tipo –el adenoasociado 8- que prácticamente es inocuo para las personas. El trabajo lo publica la revista New England Journal of Medicine.
En el ensayo se probaron distintas concentraciones de virus, y se aplicaron dos inyecciones a los voluntarios. Los cuatro que recibieron mayores cantidades consiguieron aumentar su producción de factor de coagulación hasta el 12% de lo normal y durante al menos 20 semanas. Con ello los médicos consideran que una persona no necesita tratamiento (un par de inyecciones a la semana).
El ensayo se hizo con tan pocos pacientes porque es solo una primera fase, cuyo objetivo es medir la seguridad, pero los resultados han sido tan buenos que apuntan a una prometedora vía en la que se espera con una sola inyección poder tratar a los pacientes.
**Publicado en "EL PAIS"
En el trabajo, se utilizó un virus de la familia de los adenovirus para introducir una copia buena del gen en los pacientes. Estos microorganismos tienen la propiedad de que integran su ADN en el de las personas que infectan, y, en este caso concreto , se utilizó un tipo –el adenoasociado 8- que prácticamente es inocuo para las personas. El trabajo lo publica la revista New England Journal of Medicine.
En el ensayo se probaron distintas concentraciones de virus, y se aplicaron dos inyecciones a los voluntarios. Los cuatro que recibieron mayores cantidades consiguieron aumentar su producción de factor de coagulación hasta el 12% de lo normal y durante al menos 20 semanas. Con ello los médicos consideran que una persona no necesita tratamiento (un par de inyecciones a la semana).
El ensayo se hizo con tan pocos pacientes porque es solo una primera fase, cuyo objetivo es medir la seguridad, pero los resultados han sido tan buenos que apuntan a una prometedora vía en la que se espera con una sola inyección poder tratar a los pacientes.
**Publicado en "EL PAIS"
Scientists develop vaccine that attacks breast cancer in mice
Researchers from the University of Georgia and the Mayo Clinic in Arizona have developed a vaccine that dramatically reduces tumors in a mouse model that mimics 90 percent of human breast and pancreatic cancer cases-including those resistant to common treatments. The vaccine, described this week in the early edition of the journal Proceedings of the National Academy of Sciences, reveals a promising new strategy for treating cancers that share the same distinct carbohydrate signature, including ovarian and colorectal cancers.
"This vaccine elicits a very strong immune response," said study co-senior author Geert-Jan Boons, Franklin Professor of Chemistry and a researcher in the UGA Cancer Center and its Complex Carbohydrate Research Center. "It activates all three components of the immune system to reduce tumor size by an average of 80 percent."
When cells become cancerous, the sugars on their surface proteins undergo distinct changes that set them apart from healthy cells. For decades, scientists have tried to enable the immune system to recognize those differences to destroy cancer cells rather than normal cells. But since cancer cells originate within the body, the immune system generally doesn't recognize them as foreign and therefore doesn't mount an attack.
The researchers used unique mice developed by Sandra Gendler, Grohne Professor of Therapeutics for Cancer Research at the Mayo Clinic and co-senior author on the study. Like humans, the mice develop tumors that overexpress a protein known as MUC1 on the surface of their cells. The tumor-associated MUC1 protein is adorned with a distinctive, shorter set of carbohydrates that set it apart from healthy cells.
"This is the first time that a vaccine has been developed that trains the immune system to distinguish and kill cancer cells based on their different sugar structures on proteins such as MUC1," Gendler said. "We are especially excited about the fact that MUC1 was recently recognized by the National Cancer Institute as one of the three most important tumor proteins for vaccine development."
Gendler pointed out that MUC1 is found on more than 70 percent of all cancers that kill. Many cancers, such as breast, pancreatic, ovarian and multiple myeloma, express MUC1 with the shorter carbohydrate in more than 90 percent of cases.
She explained that when cancer occurs, the architecture of the cell changes and MUC1 is produced at high levels, promoting tumor formation. A vaccine directed against MUC1 has tremendous potential, Gendler said, as a preventative for recurrence or as a prophylactic in patients at high risk for particular cancers. A vaccine also can be used together with standard therapy such as chemotherapy in cancers that cannot be cured by surgery, such as pancreatic cancer.
Boons noted that MUC1 also is overexpressed in 90 percent of the subset of patients who are not responsive to hormonal therapy, such as Tamoxifen or aromatase inhibitors, or the drug Herceptin. These so-called "triple-negative" tumors are extremely aggressive and difficult to treat, Boons said, and a new treatment option is urgently needed.
"In the U.S. alone, there are 35,000 patients diagnosed every year whose tumors are triple-negative," Boons said. "So we might have a therapy for a large group of patients for which there is currently no drug therapy aside from chemotherapy."
Therapeutic vaccines received renewed attention last year when the Food and Drug Administration approved the first cancer treatment vaccine, a drug known as Provenge that is used to treat metastatic prostate cancer. Treatment with Provenge, which is manufactured in Georgia, requires clinicians to isolate immune cells from the patient and then to send the cells to a lab, where they are linked to a protein that stimulates the immune system. The cells are returned to the patient's treating physician, who then infuses the drug over three treatments, usually two weeks apart.
Boons' vaccine, on the other hand, is much simpler. It is fully synthetic, meaning that its components can be manufactured in a lab with assembly-line precision. The vaccine consists of three components-an immune system booster known as an adjuvant, a component that triggers the production of the immune system's T-helper cells, and a carbohydrate-linked peptide molecule that directs the immune response to cells bearing MUC1 proteins with truncated carbohydrates.
Biotechnology is a key industry in Georgia, and this year Boons founded Athens-based company Viamune to help develop and commercialize the vaccine and the technologies used to create it. The company is one of nearly 30 that are affiliated with the University's BioBusiness Center, which is an incubator for life sciences start-up companies associated with UGA.
"Companies like these have the potential to create stable, high-paying jobs that have a significant social and economic impact," said Stefan Schulze, associate director of the Georgia BioBusiness Center. He noted that Viamune was a one four finalists selected from 40 companies at an investor's forum hosted this year by the non-profit organization Southeast BIO.
Boons, Gendler and their colleagues are currently testing the vaccine's effectiveness against human cancer cells in culture and are planning to assess its toxicity. If all goes well, they anticipate that phase I clinical trials to test the safety of the vaccine could begin by late 2013.
The vaccine represents nearly a decade of work on the part of Boons and his team. A 2007 study demonstrated the vaccine's effectiveness in another mouse model, and Boons is cautiously optimistic about his most recent results. Although promising results in mice often don't translate to humans, Boons said he is confident that vaccines that target the specific carbohydrate signatures of cancer cells will ultimately play an important role in the treatment of the disease.
"We are beginning to have therapies that can teach our immune system to fight what is uniquely found in cancer cells," Boons said. "When combined with early diagnosis, the hope is that one day cancer will become a manageable disease."
"This vaccine elicits a very strong immune response," said study co-senior author Geert-Jan Boons, Franklin Professor of Chemistry and a researcher in the UGA Cancer Center and its Complex Carbohydrate Research Center. "It activates all three components of the immune system to reduce tumor size by an average of 80 percent."
When cells become cancerous, the sugars on their surface proteins undergo distinct changes that set them apart from healthy cells. For decades, scientists have tried to enable the immune system to recognize those differences to destroy cancer cells rather than normal cells. But since cancer cells originate within the body, the immune system generally doesn't recognize them as foreign and therefore doesn't mount an attack.
The researchers used unique mice developed by Sandra Gendler, Grohne Professor of Therapeutics for Cancer Research at the Mayo Clinic and co-senior author on the study. Like humans, the mice develop tumors that overexpress a protein known as MUC1 on the surface of their cells. The tumor-associated MUC1 protein is adorned with a distinctive, shorter set of carbohydrates that set it apart from healthy cells.
"This is the first time that a vaccine has been developed that trains the immune system to distinguish and kill cancer cells based on their different sugar structures on proteins such as MUC1," Gendler said. "We are especially excited about the fact that MUC1 was recently recognized by the National Cancer Institute as one of the three most important tumor proteins for vaccine development."
Gendler pointed out that MUC1 is found on more than 70 percent of all cancers that kill. Many cancers, such as breast, pancreatic, ovarian and multiple myeloma, express MUC1 with the shorter carbohydrate in more than 90 percent of cases.
She explained that when cancer occurs, the architecture of the cell changes and MUC1 is produced at high levels, promoting tumor formation. A vaccine directed against MUC1 has tremendous potential, Gendler said, as a preventative for recurrence or as a prophylactic in patients at high risk for particular cancers. A vaccine also can be used together with standard therapy such as chemotherapy in cancers that cannot be cured by surgery, such as pancreatic cancer.
Boons noted that MUC1 also is overexpressed in 90 percent of the subset of patients who are not responsive to hormonal therapy, such as Tamoxifen or aromatase inhibitors, or the drug Herceptin. These so-called "triple-negative" tumors are extremely aggressive and difficult to treat, Boons said, and a new treatment option is urgently needed.
"In the U.S. alone, there are 35,000 patients diagnosed every year whose tumors are triple-negative," Boons said. "So we might have a therapy for a large group of patients for which there is currently no drug therapy aside from chemotherapy."
Therapeutic vaccines received renewed attention last year when the Food and Drug Administration approved the first cancer treatment vaccine, a drug known as Provenge that is used to treat metastatic prostate cancer. Treatment with Provenge, which is manufactured in Georgia, requires clinicians to isolate immune cells from the patient and then to send the cells to a lab, where they are linked to a protein that stimulates the immune system. The cells are returned to the patient's treating physician, who then infuses the drug over three treatments, usually two weeks apart.
Boons' vaccine, on the other hand, is much simpler. It is fully synthetic, meaning that its components can be manufactured in a lab with assembly-line precision. The vaccine consists of three components-an immune system booster known as an adjuvant, a component that triggers the production of the immune system's T-helper cells, and a carbohydrate-linked peptide molecule that directs the immune response to cells bearing MUC1 proteins with truncated carbohydrates.
Biotechnology is a key industry in Georgia, and this year Boons founded Athens-based company Viamune to help develop and commercialize the vaccine and the technologies used to create it. The company is one of nearly 30 that are affiliated with the University's BioBusiness Center, which is an incubator for life sciences start-up companies associated with UGA.
"Companies like these have the potential to create stable, high-paying jobs that have a significant social and economic impact," said Stefan Schulze, associate director of the Georgia BioBusiness Center. He noted that Viamune was a one four finalists selected from 40 companies at an investor's forum hosted this year by the non-profit organization Southeast BIO.
Boons, Gendler and their colleagues are currently testing the vaccine's effectiveness against human cancer cells in culture and are planning to assess its toxicity. If all goes well, they anticipate that phase I clinical trials to test the safety of the vaccine could begin by late 2013.
The vaccine represents nearly a decade of work on the part of Boons and his team. A 2007 study demonstrated the vaccine's effectiveness in another mouse model, and Boons is cautiously optimistic about his most recent results. Although promising results in mice often don't translate to humans, Boons said he is confident that vaccines that target the specific carbohydrate signatures of cancer cells will ultimately play an important role in the treatment of the disease.
"We are beginning to have therapies that can teach our immune system to fight what is uniquely found in cancer cells," Boons said. "When combined with early diagnosis, the hope is that one day cancer will become a manageable disease."
*Source: University of Georgia
Un marcador predice si un paciente podrá dejar los inmunosupresores
Algunos pacientes pueden prescindir de los medicamentos inmunosupresores tras haber recibido un trasplante de hígado, y librarse así de sus numerosos efectos secundarios. Pero, hasta ahora, no era posible determinar qué personas eran candidatas a dejar de tomar estos fármacos. Un nuevo estudio europeo, dirigido desde Barcelona, ha hallado un marcador en la sangre que podría usarse con este fin en un futuro cercano.
Para realizar el estudio, publicado en 'The Journal of Clinical Investigation', se reclutó a 75 voluntarios que habían pasado por un trasplante de hígado y se les sometió a periodos controlados sin medicación inmunosupresora, de entre seis y nueve meses. Antes de estas pruebas, se habían estudiado el genoma y las características inmunes de los participantes, de forma que se pudiera hallar cuáles eran las diferencias entre quienes toleraban el abandono de fármacos y quienes no podían prescindir de ellos.
Tal y como esperaban, los investigadores pudieron detectar un marcador, presente tanto en la sangre como en el propio hígado, que distingue a los pacientes que van a ser capaces de sobrevivir sin inmunosupresión. Se trata de de dos proteínas -hepcidina y ferritina- involucradas en el metabolismo del hierro, presentes en mayores niveles en las personas tolerantes al abandono de los fármacos. Es la primera vez que estas proteínas se relacionan con la función del sistema inmune, aunque algunos estudios con animales ya las habían relacionado con los procesos de inflamación.
El doctor Alberto Fernández-Fueyo, experto en Hepatología del Hospital Clínic de Barcelona y uno de los firmantes de la investigación, ha señalado a ELMUNDO.es que estos marcadores son "la herramienta más fiable que existe para identificar a pacientes que podrían prescindir de la inmunodepresión", algo que podría ser posible de aquí "a tres o cuatro años". Primero hará falta un estudio más grande para confirmar los resultados, admite este especialista, aunque una empresa de Francia ya ha comenzado a elaborar un test para detectar a estos pacientes.
-Manipular el metabolismo
Lo que no está claro aún es cómo se podría intervenir sobre el resto de pacientes para lograr que sean igualmente capaces de sobrevivir sin medicamentos. "Hay que investigar si manipulando el metabolismo del hierro se logra que un porcentaje mayor se beneficie", indica Fernández-Fueyo. Para ello, habría dos posibles vías: los fármacos o la activación de genes, siempre con el fin de que estas proteínas se expresen en las cantidades necesarias.
En otra clase de trasplantes, sería imposible realizar estudios como este, según comenta el investigador español. Se sabe, por ejemplo, que pacientes con un trasplante renal han sobrevivido sin inmunosupresores, pero su porcentaje es mínimo, y los casos detectados han sido personas que han renunciado a los fármacos por otros motivos, nunca como parte de un estudio. En cualquier caso, la posibilidad de inducir tolerancia al nuevo órgano es "el santo grial de la investigación en trasplantes", explica este experto, ya que los pacientes podrían pasar el resto de sus vidas sin depender de los medicamentos.
**Publicado en "EL MUNDO"
Para realizar el estudio, publicado en 'The Journal of Clinical Investigation', se reclutó a 75 voluntarios que habían pasado por un trasplante de hígado y se les sometió a periodos controlados sin medicación inmunosupresora, de entre seis y nueve meses. Antes de estas pruebas, se habían estudiado el genoma y las características inmunes de los participantes, de forma que se pudiera hallar cuáles eran las diferencias entre quienes toleraban el abandono de fármacos y quienes no podían prescindir de ellos.
Tal y como esperaban, los investigadores pudieron detectar un marcador, presente tanto en la sangre como en el propio hígado, que distingue a los pacientes que van a ser capaces de sobrevivir sin inmunosupresión. Se trata de de dos proteínas -hepcidina y ferritina- involucradas en el metabolismo del hierro, presentes en mayores niveles en las personas tolerantes al abandono de los fármacos. Es la primera vez que estas proteínas se relacionan con la función del sistema inmune, aunque algunos estudios con animales ya las habían relacionado con los procesos de inflamación.
El doctor Alberto Fernández-Fueyo, experto en Hepatología del Hospital Clínic de Barcelona y uno de los firmantes de la investigación, ha señalado a ELMUNDO.es que estos marcadores son "la herramienta más fiable que existe para identificar a pacientes que podrían prescindir de la inmunodepresión", algo que podría ser posible de aquí "a tres o cuatro años". Primero hará falta un estudio más grande para confirmar los resultados, admite este especialista, aunque una empresa de Francia ya ha comenzado a elaborar un test para detectar a estos pacientes.
-Manipular el metabolismo
Lo que no está claro aún es cómo se podría intervenir sobre el resto de pacientes para lograr que sean igualmente capaces de sobrevivir sin medicamentos. "Hay que investigar si manipulando el metabolismo del hierro se logra que un porcentaje mayor se beneficie", indica Fernández-Fueyo. Para ello, habría dos posibles vías: los fármacos o la activación de genes, siempre con el fin de que estas proteínas se expresen en las cantidades necesarias.
En otra clase de trasplantes, sería imposible realizar estudios como este, según comenta el investigador español. Se sabe, por ejemplo, que pacientes con un trasplante renal han sobrevivido sin inmunosupresores, pero su porcentaje es mínimo, y los casos detectados han sido personas que han renunciado a los fármacos por otros motivos, nunca como parte de un estudio. En cualquier caso, la posibilidad de inducir tolerancia al nuevo órgano es "el santo grial de la investigación en trasplantes", explica este experto, ya que los pacientes podrían pasar el resto de sus vidas sin depender de los medicamentos.
**Publicado en "EL MUNDO"
Researchers use new finding to clear bloodstream malaria infection in mice
University of Iowa researchers and colleagues have discovered how malaria manipulates the immune system to allow the parasite to persist in the bloodstream. By rescuing this immune system pathway, the research team was able to cure mice of bloodstream malaria infections. The findings, which were published December 11 in the Advance Online Publication of the journal Nature Immunology, could point the way to a new approach for treating malaria that does not rely on vaccination and is not susceptible to the parasite's notorious ability to develop drug resistance.
"Malaria is chronic, prolonged infection and the host immune defense has a tough time clearing it and sometimes it never clears it," says Noah Butler, PhD, UI postdoctoral research scholar and lead study author. "We've determined that this prolonged infection actually drives dysfunction of the immune cells that are supposed to be fighting the infection, which in essence allows further persistence of the parasite infection."
More specifically, the study showed that the malaria parasite stimulate these key immune cells (known as CD4+ T cells) so that they continuously express molecules called inhibitory receptors. Under normal circumstances, these molecules help to "apply the brakes" to the immune response and prevent over-activation that can be harmful. However, by keeping the mechanism turned on, the malaria parasite damps down the immune response significantly, reducing the T cells' ability to fight the parasite and allowing it to persist.
Importantly, the team also showed that blocking the action of the inhibitory receptor molecules resulted in immediate and complete clearance of the malaria parasite.
"When we blocked the function of these molecules, we took the brakes off the host's immune response and everything got better -- the overall immune response was dramatically improved and there was immediate control and accelerated clearance of the parasite," says John Harty, PhD, professor of microbiology and pathology at the UI Carver College of Medicine and senior study author. "These findings suggest an alternative approach for the treatment of existing malaria infection."
-200 Million Malaria Cases
More than half the world's population is at risk of malaria, a mosquito-borne parasite that causes anemia and high fever and which can persist for weeks or months. There are more than 200 million cases of malaria each year and an estimated 800,000 children die from malaria annually.
Harty notes that the current study was done in mice and it is not yet known if the same approach will work in humans. However, two factors suggest the strategy may have potential. First, drugs that block inhibitory receptor molecules are available and currently being tested as cancer therapies. And second, the UI team found that malaria infection in humans does lead to increased expression of inhibitory receptors on CD4+ T cells suggesting that these molecules could represent a viable target for human therapies.
The human findings were the product of an important collaboration between the UI team and malaria researchers working in the sub-Saharan country of Mali. The Mali team based at the University of Bamako works in a sophisticated lab set up by the National Institutes of Health. In Mali's dry season there are no mosquitoes, so there's no malaria; in the wet season, the mosquitoes come out and malaria appears.
"Workers in the NIH lab obtained blood samples from malaria-free children at the end of the dry season, and then when some of the children returned to the clinic with malaria at the beginning of the next wet season they were treated immediately and the workers also took a second blood sample," Harty explains. "This allowed us to analyze the blood for expression of this inhibitory molecule before and after infection and we found that the molecule went up after infection."
**Source: University of Iowa Health Care
"Malaria is chronic, prolonged infection and the host immune defense has a tough time clearing it and sometimes it never clears it," says Noah Butler, PhD, UI postdoctoral research scholar and lead study author. "We've determined that this prolonged infection actually drives dysfunction of the immune cells that are supposed to be fighting the infection, which in essence allows further persistence of the parasite infection."
More specifically, the study showed that the malaria parasite stimulate these key immune cells (known as CD4+ T cells) so that they continuously express molecules called inhibitory receptors. Under normal circumstances, these molecules help to "apply the brakes" to the immune response and prevent over-activation that can be harmful. However, by keeping the mechanism turned on, the malaria parasite damps down the immune response significantly, reducing the T cells' ability to fight the parasite and allowing it to persist.
Importantly, the team also showed that blocking the action of the inhibitory receptor molecules resulted in immediate and complete clearance of the malaria parasite.
"When we blocked the function of these molecules, we took the brakes off the host's immune response and everything got better -- the overall immune response was dramatically improved and there was immediate control and accelerated clearance of the parasite," says John Harty, PhD, professor of microbiology and pathology at the UI Carver College of Medicine and senior study author. "These findings suggest an alternative approach for the treatment of existing malaria infection."
-200 Million Malaria Cases
More than half the world's population is at risk of malaria, a mosquito-borne parasite that causes anemia and high fever and which can persist for weeks or months. There are more than 200 million cases of malaria each year and an estimated 800,000 children die from malaria annually.
Harty notes that the current study was done in mice and it is not yet known if the same approach will work in humans. However, two factors suggest the strategy may have potential. First, drugs that block inhibitory receptor molecules are available and currently being tested as cancer therapies. And second, the UI team found that malaria infection in humans does lead to increased expression of inhibitory receptors on CD4+ T cells suggesting that these molecules could represent a viable target for human therapies.
The human findings were the product of an important collaboration between the UI team and malaria researchers working in the sub-Saharan country of Mali. The Mali team based at the University of Bamako works in a sophisticated lab set up by the National Institutes of Health. In Mali's dry season there are no mosquitoes, so there's no malaria; in the wet season, the mosquitoes come out and malaria appears.
"Workers in the NIH lab obtained blood samples from malaria-free children at the end of the dry season, and then when some of the children returned to the clinic with malaria at the beginning of the next wet season they were treated immediately and the workers also took a second blood sample," Harty explains. "This allowed us to analyze the blood for expression of this inhibitory molecule before and after infection and we found that the molecule went up after infection."
**Source: University of Iowa Health Care
Un meta-análisis concluye que beber aumenta el sexo sin protección
Ya es oficial. La investigación científica acaba de demostrar que el consumo de alcohol, por sí solo y sin tener en cuenta otros factores de riesgo, aumenta las posibilidades de tener sexo sin protección y, por lo tanto, también incrementa la incidencia de enfermedades de transmisión sexual.
Muchos trabajos habían apuntado que la desinhibición que provoca el alcohol hace que la persona que lo consume adopte comportamientos más arriesgados, en los que no incurriría si está sobria. Pero hasta ahora no se había demostrado que estas bebidas fueran una causa directa e independiente de los encuentros sin condón. Una revisión de 12 estudios, publicada en 'Addiction', corrobora esta relación de causalidad y señala que un incremento de 0,1mg/ml de alcohol en sangre aumenta un 5% las posibilidades de tener sexo de riesgo.
Los autores, de distintas instituciones de salud de Canadá y EEUU, se centraron en analizar la intención de utilizar preservativo -no el hecho mismo de usarlo- en jóvenes que fueron asignados a dos grupos. Uno de ellos bebía alcohol y el otro no. Así comprobaron que el alcohol afecta enseguida a la toma de decisiones y cuanto más bebe uno, más riesgo de tener relaciones desprotegidas.
El efecto observado no tuvo que ver con la personalidad del individuo, si es más compulsivo o se siente atraído por el peligro, por lo que los investigadores concluyen que el alcohol por sí solo es responsable de muchos encuentros sexuales sin condón.
"Este hallazgo debería tenerse en cuenta en los programas de prevención del VIH y otras enfermedades de transmisión sexual", comenta el doctor Jürgen Rehm, del Centro de Adicciones y Salud Mental de Toronto y coordinador del análisis.
"Nuestros resultados explican en parte por qué las nuevas infecciones por VIH se mantienen más o menos estables en los países desarrollados, a pesar de la información que tienen los ciudadanos. El alcohol, que afecta al juicio, puede estar detrás del problema, ya que la transmisión sexual del virus se ha convertido en la vía más frecuente", añade.
**Publicado en "EL MUNDO"
Muchos trabajos habían apuntado que la desinhibición que provoca el alcohol hace que la persona que lo consume adopte comportamientos más arriesgados, en los que no incurriría si está sobria. Pero hasta ahora no se había demostrado que estas bebidas fueran una causa directa e independiente de los encuentros sin condón. Una revisión de 12 estudios, publicada en 'Addiction', corrobora esta relación de causalidad y señala que un incremento de 0,1mg/ml de alcohol en sangre aumenta un 5% las posibilidades de tener sexo de riesgo.
Los autores, de distintas instituciones de salud de Canadá y EEUU, se centraron en analizar la intención de utilizar preservativo -no el hecho mismo de usarlo- en jóvenes que fueron asignados a dos grupos. Uno de ellos bebía alcohol y el otro no. Así comprobaron que el alcohol afecta enseguida a la toma de decisiones y cuanto más bebe uno, más riesgo de tener relaciones desprotegidas.
El efecto observado no tuvo que ver con la personalidad del individuo, si es más compulsivo o se siente atraído por el peligro, por lo que los investigadores concluyen que el alcohol por sí solo es responsable de muchos encuentros sexuales sin condón.
"Este hallazgo debería tenerse en cuenta en los programas de prevención del VIH y otras enfermedades de transmisión sexual", comenta el doctor Jürgen Rehm, del Centro de Adicciones y Salud Mental de Toronto y coordinador del análisis.
"Nuestros resultados explican en parte por qué las nuevas infecciones por VIH se mantienen más o menos estables en los países desarrollados, a pesar de la información que tienen los ciudadanos. El alcohol, que afecta al juicio, puede estar detrás del problema, ya que la transmisión sexual del virus se ha convertido en la vía más frecuente", añade.
**Publicado en "EL MUNDO"
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