Laquinimod is an orally available synthetic compound that has been successfully evaluated in phase II/III clinical studies for the treatment of relapsing-remitting multiple sclerosis (RRMS). The mechanism of action of laquinimod has not been fully elucidated, but a study published in the January 2012 issue of The American Journal of Pathology suggests that laquinimod triggers immune cells within the central nervous system to produce and release brain-derived neurotrophic factor (BDNF), contributing to the repair or survival of neurons and thus limiting brain damage. "Our data are indicative of a direct and sustained effect of laquinimod on the up-regulation of bioactive BDNF in patients with RRMS. Additionally, we demonstrate that laquinimod targets monocytes and skews the phagocyte population towards a regulatory phenotype, which in turn mediates immune modulation in vivo," explained Jan Thöne, MD, of the Department of Neurology at St. Josef-Hospital Bochum and Ruhr-University Bochum, Germany.
Neurotrophins, such as BDNF, are essential for the development and maintenance of neurons and axons in the central nervous system. Although BDNF is mainly produced by neurons, several types of immune cells also secrete BDNF, suggesting a role in neuroprotection.
To elucidate the mechanism of action of laquinimod, and to explore its potential neuroprotective capacity, the researchers evaluated levels of BDNF in the serum of RRMS patients treated with laquinimod in phase II clinical trials. A significant and robust BDNF increase occurred in 76% of the laquinimod-treated patients, with up to an 11-fold increase in BDNF serum levels observed in individual patients. BDNF elevation in individual patients was independent of relapse rate, and there was no correlation between BDNF levels and age, gender, or baseline disability. Yet, the source of serum BDNF subsequent to treatment remained questionable.
Experiments with animal models corroborated the findings in human patients. Experimental autoimmune encephalomyelitis (EAE; a model of MS) was induced in mice with a conditional BDNF deficiency in immune cells (LLF mice) and in wild-type (WT) control mice. Treatment with laquinimod resulted in a significant reduction in EAE incidence and disease severity in the WT mice. The effect of laquinimod was significantly reduced in the LLF-mice.
Further studies showed that WT mice treated with a suboptimal dose of laquinimod demonstrated a significant reduction in the inflammatory area and level of demyelination. These mice also displayed a reduction of macrophage infiltration and a significant preservation of axonal densities in comparison with laquinimod-treated LLF mice and controls. The data suggest a BDNF-dependent mechanism of action for laquinimod in autoimmune demyelination.
To investigate whether laquinimod-treated monocytes mediate immune modulation in vivo, laquinimod-stimulated monocytes were injected into WT mice at an early EAE disease stage. The mice showed less severe disease course than controls. Transfer of laquinimod-treated cells derived from LLF mice into WT mice with ongoing EAE did not influence disease course. The cells also secrete significantly less IL-10, an immunomodulatory cytokine that is associated with the generation of regulatory monocytes.
"Consistent with immunomodulatory properties, laquinimod skewed monocytes towards a regulatory phenotype and also acted via modulation of BDNF, which may contribute to neuroprotection in MS patients," said Dr. Thöne. "To date, selective targeting of monocytes has not been described for any other MS pipeline drug, highlighting an innovative mechanism of action of laquinimod."
**Source: Elsevier
07 December 2011
Un reportaje de la cotizada maniquí Karlie Kloss reaviva la polémica sobre la anorexia en la industria de la moda
Un reportaje gráfico de Karlie Kloss, modelo estadounidense de 19 años y nueva reina de la moda internacional, ha despertado la polémica. Kloss, que se formó como bailarina, es desde 2008 una de las maniquíes más cotizadas del mundo. Presencia fija en los desfiles de Milán, Nueva York y París, ha sido imagen de Dior y Marc Jacobs y, desde este año, forma parte del elenco de la marca de lencería Victoria's Secret. Pero las imágenes de la supermodelo que Steven Meisel publica en el último número de Vogue Italia han disparado las alarmas. En ellas se muestran torsiones que potencian la impresión ante un enflaquecido cuerpo y dejan aflorar costillas y músculos bajo su piel desnuda.
Parte del problema es que el reportaje aparece bajo el nombre de The new body (El nuevo cuerpo). Un título cuanto menos ambiguo que ha desatado inmediatas críticas en Italia por reavivar el viejo fantasma de la anorexia en la industria de la moda. Tanto que la más controvertida de las fotografías -en la que la modelo aparece enfundada en unos ceñidos shorts- desapareció de la versión online de la revista. Pero ya era demasiado tarde para frenar el debate: blogs y comentarios en la web de la publicación han polemizado tanto por las imágenes de Meisel como por el hecho de que la modelo sea presentada como el prototipo físico más deseable.
"Pero ¿a dónde fue a parar vuestra campaña contra la anorexia? ¡Hipócritas!", se indigna una lectora en Vogue.it. "Consideramos que la modelo Karlie Kloss luce un cuerpo musculoso y tonificado, que nada tiene que ver con la anorexia", se defiende la redacción en un comentario publicado al hilo de los de sus lectores, en la misma página web. "Si una revista como Vogue tuviera que publicar solo cuerpos normales sería mejor cerrarla. Sería como si en tiempos de crisis, como estos, no se pudiesen publicitar joyas o prendas de lujo: significaría dejar de soñar", comenta Laura, otra lectora. Enseguida le contesta otra: "A mí estas imágenes no me suscitan ningunas ganas de soñar, al revés, me comunican dureza, constricción".
El debate continúa en la Red. Muchos internautas se sienten traicionados ya que precisamente la edición italiana de Vogue había emprendido una campaña para que se cerraran las páginas web que fomentaban la anorexia. Lo cierto es que el mismo Meisel firmaba el tema de portada de junio, con una secuencia titulada Belle vere (Guapas auténticas). Retrataba voluptuosas modelos, muy alejadas de Koss, como Tara Lynn, Candice Huffine y Robyn Lawley. Aparecían orgullosas de sus grandes pechos y de sus contundentes caderas en imágenes de intrigante sensualidad.
Franca Sozzani, la directora de la revista, fue alabada entonces como abogada de la causa antianorexia, porque desde sus páginas exaltaba la variedad de la belleza del cuerpo femenino y mostraba que el modelo de la extrema delgadez impuesto entre focos y pasarelas no es el único posible. Sin embargo, seis meses después Sozzani es vapuleada por mostrar otro tipo de anatomía.
"Pero ¿a dónde fue a parar vuestra campaña contra la anorexia? ¡Hipócritas!", se indigna una lectora en Vogue.it. "Consideramos que la modelo Karlie Kloss luce un cuerpo musculoso y tonificado, que nada tiene que ver con la anorexia", se defiende la redacción en un comentario publicado al hilo de los de sus lectores, en la misma página web. "Si una revista como Vogue tuviera que publicar solo cuerpos normales sería mejor cerrarla. Sería como si en tiempos de crisis, como estos, no se pudiesen publicitar joyas o prendas de lujo: significaría dejar de soñar", comenta Laura, otra lectora. Enseguida le contesta otra: "A mí estas imágenes no me suscitan ningunas ganas de soñar, al revés, me comunican dureza, constricción".
El debate continúa en la Red. Muchos internautas se sienten traicionados ya que precisamente la edición italiana de Vogue había emprendido una campaña para que se cerraran las páginas web que fomentaban la anorexia. Lo cierto es que el mismo Meisel firmaba el tema de portada de junio, con una secuencia titulada Belle vere (Guapas auténticas). Retrataba voluptuosas modelos, muy alejadas de Koss, como Tara Lynn, Candice Huffine y Robyn Lawley. Aparecían orgullosas de sus grandes pechos y de sus contundentes caderas en imágenes de intrigante sensualidad.
Franca Sozzani, la directora de la revista, fue alabada entonces como abogada de la causa antianorexia, porque desde sus páginas exaltaba la variedad de la belleza del cuerpo femenino y mostraba que el modelo de la extrema delgadez impuesto entre focos y pasarelas no es el único posible. Sin embargo, seis meses después Sozzani es vapuleada por mostrar otro tipo de anatomía.
**Publicado en "EL PAIS"
Defensive measures: Toward a vaccine for Ebola
On Aug. 26, 1976, a time bomb exploded in Yambuku, a remote village in Zaire, (now the Democratic Republic of the Congo). A threadlike virus known as Ebola had emerged, soon earning a grim distinction as one of the most lethal, naturally occurring pathogens on earth, killing up to 90 percent of its victims, and producing a terrifying constellation of symptoms known as hemorrhagic fever. Now, Charles Arntzen, a researcher at the Biodesign Institute at Arizona State University, along with colleagues from ASU, the University of Arizona College of Medicine-Phoenix, and the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, have made progress toward a vaccine against the deadly virus.
The group's research results appear in the Proceedings of the National Academy of Sciences, along with a companion paper by their collaborators at Mapp Pharmaceuticals in San Diego, CA, led by Larry Zeitlin. Arntzen's group demonstrated that a plant-derived vaccine for Ebola provided strong immunological protection in a mouse model.
If early efforts bear fruit, an Ebola vaccine could be stockpiled for use in the United States, should the country fall victim to a natural outbreak or a bioterrorism event in which a weaponized strain of the virus were unleashed on soldiers or the public.
To date, Ebola outbreaks have been mercifully rare. For researchers like Arntzen however, this presents a challenge: "With other lethal viruses like HIV there is a common pattern of occurrence, allowing for vaccine testing. For example, an AIDS vaccine study is now underway at two locations in Thailand, which were chosen because of a current high incidence of the disease."
By contrast, Ebola events are fleeting, episodic and largely unpredictable. For this reason, Arntzen stresses that an Ebola vaccine would most likely not be used prophylactically -- that is, as a means of protecting large populations, as in the case of common vaccines against diseases like influenza or polio. Instead, the idea is to have a sizeable store of the vaccine on hand in the event of a sudden outbreak, either natural or nefarious.
The group's research results appear in the Proceedings of the National Academy of Sciences, along with a companion paper by their collaborators at Mapp Pharmaceuticals in San Diego, CA, led by Larry Zeitlin. Arntzen's group demonstrated that a plant-derived vaccine for Ebola provided strong immunological protection in a mouse model.
If early efforts bear fruit, an Ebola vaccine could be stockpiled for use in the United States, should the country fall victim to a natural outbreak or a bioterrorism event in which a weaponized strain of the virus were unleashed on soldiers or the public.
To date, Ebola outbreaks have been mercifully rare. For researchers like Arntzen however, this presents a challenge: "With other lethal viruses like HIV there is a common pattern of occurrence, allowing for vaccine testing. For example, an AIDS vaccine study is now underway at two locations in Thailand, which were chosen because of a current high incidence of the disease."
By contrast, Ebola events are fleeting, episodic and largely unpredictable. For this reason, Arntzen stresses that an Ebola vaccine would most likely not be used prophylactically -- that is, as a means of protecting large populations, as in the case of common vaccines against diseases like influenza or polio. Instead, the idea is to have a sizeable store of the vaccine on hand in the event of a sudden outbreak, either natural or nefarious.
-A killer up close
Ebola belongs to a family of viruses known as filoviridae, which take their name from their serpentine, filamentous structure. Filoviridae fall into two broad categories known as Ebola-like and Marburg-like viruses. In the original Ebola outbreak in Yambuku, situated along the Ebola River, 280 of the 318 identified cases died. Soon thereafter, an additional 284 cases and 151 deaths occurred in nearby Sudan. In Yambuku, the small local hospital was shut down, after 11 of its 17 staff members died.
The likely reservoir for the disease is bats. Primates including monkeys can become infected from eating bats or from fruit the bats may have dropped. Infected animals can then spread the disease to humans through bites, or when the primates are consumed for food -- a practice prevalent in some regions of Africa.
The course of the disease is pitiless, sometimes producing hemorrhagic fever, which causes severe bleeding from mucous membranes, including the gastroinestinal tract, eyes, nose, vagina and gingiva. The very high mortality and gruesome symptoms of the disease have riveted public attention and have been the focus of numerous films and books, notably Richard Preston's The Hot Zone.
Arntzen notes that while no human vaccine against Ebola currently exists, a number of strong candidates have emerged. While some have yielded good results in animal models, in terms of protection against the virus, they have practical shortcomings. "All of these existing vaccine candidates are genetically modified live viruses," he says. Vaccines of this sort require very careful conditions of storage and have a tendency to lose potency over a period of months. "If you've got something that you're going to have to keep at liquid nitrogen temperatures for years at a time, in hopes that there will never be an outbreak, it makes it impractical. "
Ebola belongs to a family of viruses known as filoviridae, which take their name from their serpentine, filamentous structure. Filoviridae fall into two broad categories known as Ebola-like and Marburg-like viruses. In the original Ebola outbreak in Yambuku, situated along the Ebola River, 280 of the 318 identified cases died. Soon thereafter, an additional 284 cases and 151 deaths occurred in nearby Sudan. In Yambuku, the small local hospital was shut down, after 11 of its 17 staff members died.
The likely reservoir for the disease is bats. Primates including monkeys can become infected from eating bats or from fruit the bats may have dropped. Infected animals can then spread the disease to humans through bites, or when the primates are consumed for food -- a practice prevalent in some regions of Africa.
The course of the disease is pitiless, sometimes producing hemorrhagic fever, which causes severe bleeding from mucous membranes, including the gastroinestinal tract, eyes, nose, vagina and gingiva. The very high mortality and gruesome symptoms of the disease have riveted public attention and have been the focus of numerous films and books, notably Richard Preston's The Hot Zone.
Arntzen notes that while no human vaccine against Ebola currently exists, a number of strong candidates have emerged. While some have yielded good results in animal models, in terms of protection against the virus, they have practical shortcomings. "All of these existing vaccine candidates are genetically modified live viruses," he says. Vaccines of this sort require very careful conditions of storage and have a tendency to lose potency over a period of months. "If you've got something that you're going to have to keep at liquid nitrogen temperatures for years at a time, in hopes that there will never be an outbreak, it makes it impractical. "
-Fighting pathogens with plants
Of the vaccines available to doctors today, some (like influenza) are produced in eggs, some in cultured animal cells, and others in yeast. Arntzen's team has taken a different approach to vaccine production by converting tobacco plants into living pharmaceutical factories. They created a DNA blueprint for their Ebola vaccine, and used a specialized bacterium to infuse it into the leaves of tobacco. "The blueprint converts each leaf cell into a miniature manufacturing unit," Arntzen says.
In the current study, the vaccine blueprint was designed by fusing a key surface protein (known as GP1) from the Ebola virus with a monoclonal antibody customized to bind to GP1. The resulting molecules' opposite ends attract each other, like a group of rod-shaped magnets. When the vaccine molecules bind to each other, they form an aggregate called an Ebola Immune Complex (EIC). "In immunology, that means you've got something that is much easier for our immune system to recognize," Arntzen says. "Because it has many copies of an identical molecule, it's called a repeating array."
Within two weeks after the vaccine "blueprint" is delivered to tobacco leaves, enough of the EIC accumulates to allow its purification from other leaf cell components. The researchers then vaccinated mice with the purified sample, and showed that their immune system gave a strong response.
For the ultimate validation of the vaccine however, it was necessary to show that the vaccinated mice could withstand an Ebola virus infection. Because of the dangers in handling the virus, these experiments were conducted by skilled researchers at a high containment facility operated by the US Army Medical Research Institute in Maryland. It was found that the level of protection of the vaccinated mice was equivalent to that seen in prior experiments with the best, previously available experimental vaccine.
The advantages of using tobacco to manufacture a vaccine are significant. The initial costs for plant growth are much cheaper than design of traditional pharmaceutical facilities. In addition, the material extracted from tobacco leaves can be easily purified, and then might be spray dried or freeze-dried, yielding a highly stable compound, storable at ambient temperatures for extended periods. This will be essential for an Ebola vaccine, since it will primarily be stockpiled to use only if there is a disease outbreak.
Vaccines typically contain adjuvants -- immune modulating factors that improve a vaccine's protective qualities. Most vaccines contain alum (or aluminum hydroxide), which is an FDA approved adjuvant. In the case of the plant-derived Ebola vaccine, alum did not improve the survival rates in mice when it was co-administered with EIC. Instead, the group found that a Toll-like receptor (TLR) agonist known as PIC, when delivered in tandem with EIC, dramatically improved survival.
Toll-like receptors are part of the body's innate immune system -- involved in processes of inflammation, where defensive cells like macrophages and dendritic cells are attracted to the site of infection. Arntzen explains that the TLR agonist PIC acts to mimic a site of inflammation, amplifying the immune response, without causing tissue damage. In experiments using a combination of PIC and EIC, mice achieved an 80 percent survival rate against a lethal challenge of Ebola -- commensurate with the best existing vaccine candidates.
Of the vaccines available to doctors today, some (like influenza) are produced in eggs, some in cultured animal cells, and others in yeast. Arntzen's team has taken a different approach to vaccine production by converting tobacco plants into living pharmaceutical factories. They created a DNA blueprint for their Ebola vaccine, and used a specialized bacterium to infuse it into the leaves of tobacco. "The blueprint converts each leaf cell into a miniature manufacturing unit," Arntzen says.
In the current study, the vaccine blueprint was designed by fusing a key surface protein (known as GP1) from the Ebola virus with a monoclonal antibody customized to bind to GP1. The resulting molecules' opposite ends attract each other, like a group of rod-shaped magnets. When the vaccine molecules bind to each other, they form an aggregate called an Ebola Immune Complex (EIC). "In immunology, that means you've got something that is much easier for our immune system to recognize," Arntzen says. "Because it has many copies of an identical molecule, it's called a repeating array."
Within two weeks after the vaccine "blueprint" is delivered to tobacco leaves, enough of the EIC accumulates to allow its purification from other leaf cell components. The researchers then vaccinated mice with the purified sample, and showed that their immune system gave a strong response.
For the ultimate validation of the vaccine however, it was necessary to show that the vaccinated mice could withstand an Ebola virus infection. Because of the dangers in handling the virus, these experiments were conducted by skilled researchers at a high containment facility operated by the US Army Medical Research Institute in Maryland. It was found that the level of protection of the vaccinated mice was equivalent to that seen in prior experiments with the best, previously available experimental vaccine.
The advantages of using tobacco to manufacture a vaccine are significant. The initial costs for plant growth are much cheaper than design of traditional pharmaceutical facilities. In addition, the material extracted from tobacco leaves can be easily purified, and then might be spray dried or freeze-dried, yielding a highly stable compound, storable at ambient temperatures for extended periods. This will be essential for an Ebola vaccine, since it will primarily be stockpiled to use only if there is a disease outbreak.
Vaccines typically contain adjuvants -- immune modulating factors that improve a vaccine's protective qualities. Most vaccines contain alum (or aluminum hydroxide), which is an FDA approved adjuvant. In the case of the plant-derived Ebola vaccine, alum did not improve the survival rates in mice when it was co-administered with EIC. Instead, the group found that a Toll-like receptor (TLR) agonist known as PIC, when delivered in tandem with EIC, dramatically improved survival.
Toll-like receptors are part of the body's innate immune system -- involved in processes of inflammation, where defensive cells like macrophages and dendritic cells are attracted to the site of infection. Arntzen explains that the TLR agonist PIC acts to mimic a site of inflammation, amplifying the immune response, without causing tissue damage. In experiments using a combination of PIC and EIC, mice achieved an 80 percent survival rate against a lethal challenge of Ebola -- commensurate with the best existing vaccine candidates.
-The road ahead
In their companion PNAS paper, Arnzen's collaborators at Mapp Biopharmaceuticals outline the process for creating the monoclonal antibodies used for this research. Treatment for an Ebola infection, Arntzen says, would likely involve the injection of fast acting antibodies to attack the virus directly -- a process known as passive immunization, combined with a vaccine to stimulate the protective immune response (active immunization). This approach is commonly used in the case of other viral infections, particularly rabies. "Our two papers offer a nice back to back picture," Arntzen says. "We can manufacture both of these post-Ebola exposure reagents for a defensive stockpile, using tobacco."
The next steps for a plant-derived filovirus vaccine will involve using the EIC platform to design protection against the full range of these threadlike viruses. The method, with its straightforward purification protocol might also be used in the case of other pathogens including hepatitis C or dengue fever, where the extraction of glycoproteins has thus far been difficult.
Should efforts succeed in producing a post-exposure therapeutic that could be stockpiled by the U.S. military, the vaccine could also be made available to the Center for Disease Control for immediate use in the event of a remote outbreak.
In their companion PNAS paper, Arnzen's collaborators at Mapp Biopharmaceuticals outline the process for creating the monoclonal antibodies used for this research. Treatment for an Ebola infection, Arntzen says, would likely involve the injection of fast acting antibodies to attack the virus directly -- a process known as passive immunization, combined with a vaccine to stimulate the protective immune response (active immunization). This approach is commonly used in the case of other viral infections, particularly rabies. "Our two papers offer a nice back to back picture," Arntzen says. "We can manufacture both of these post-Ebola exposure reagents for a defensive stockpile, using tobacco."
The next steps for a plant-derived filovirus vaccine will involve using the EIC platform to design protection against the full range of these threadlike viruses. The method, with its straightforward purification protocol might also be used in the case of other pathogens including hepatitis C or dengue fever, where the extraction of glycoproteins has thus far been difficult.
Should efforts succeed in producing a post-exposure therapeutic that could be stockpiled by the U.S. military, the vaccine could also be made available to the Center for Disease Control for immediate use in the event of a remote outbreak.
**Source: Arizona State University
Los turnos de noche aumentan el riesgo de diabetes tipo 2 en la mujer
Más divorcios, más trastornos digestivos y cardiovasculares. Según un grupo de expertos de la Escuela de Salud Pública de Harvard en Boston (EEUU), las mujeres que trabajan en turnos de noche se exponen a un riesgo más: diabetes tipo 2. Y cuantos más años se mantienen estas condiciones laborales, mayores son las probabilidades de sufrir esta afección. Así lo refleja un estudio publicado esta semana en la revista 'PLoS Medicine'.
Ya se tenían indicios sobre esta asociación, sobre todo con la obesidad y los riesgos cardiovasculares, pero "este es uno de los primeros trabajos que se basa en una cohorte tan amplia y con un seguimiento de muchos años", señala Francisco Javier Puertas, miembro de la Sociedad Española del Sueño y responsable de la Unidad del Sueño del Hospital Universitario de la Ribera (Valencia).
Frank Hu y su equipo de investigadores utilizaron los datos de dos encuestas de salud realizadas a las enfermeras en 1976 y en 1989. "Seguimos a 69.269 mujeres de la primera encuesta y a 107.915 de la segunda, todas sin diabetes, sin enfermedades cardiovasculares y sin cáncer". Del primer grupo, 6.165 desarrollaron diabetes tipo 2 y del segundo, 3.961.
Después de 20 años de seguimiento y relacionando los resultados con los turnos de noche que hacía cada enfermera, los autores de este trabajo observacional se dieron cuenta de que el riesgo de diabetes estaba muy relacionado con sus rotaciones nocturnas y esto se intensificaba a medida que pasaba el tiempo. "Comparado con las mujeres que no tenían turnos de noche, aquellas que lo mantenían entre uno o dos años, tenían un 5% más de riesgo; si tenían estos turnos durante 3-9 años, el porcentaje incrementaba a un 20% y hasta un 40% si las enfermeras se pasaban entre 10 y 19 años con estos turnos. Más de 20 años implicaba casi el 60% más de riesgo".
Como explica el especialista español al comentar este estudio, "sabemos, por modelos experimentales en adultos jóvenes, que la privación total o parcial del sueño después de una semana provoca un efecto parecido al de las personas con diabetes. Presentan problemas para absorber la glucosa, es decir, de alguna manera, genera estados prediabéticos". La cantidad y la calidad del sueño es fundamental para el correcto funcionamiento del sistema metabólico, agrega.
Como explica el experto, el descanso diurno es "poco reparador", ya que durante el día los parámetros biológicos tienen unas constantes naturales diferentes a las de la noche, en que el organismo se prepara para descansar. "Al cuerpo no se le puede engañar". En el trabajador nocturno se produce un desajuste de su ritmo "circadiano natural", lo que se traduce en una predisposición a la fatiga y la irritabilidad.
Aunque estos datos confirman una hipótesis anterior, los autores del estudio realizado en Boston reconocen que la asociación entre turnos de noche y diabetes era más débil si se tenían en cuenta otros factores como la nutrición. Generalmente, apunta el doctor Puertas, "los trabajadores nocturnos tienen menos actividad física y comen a deshoras (nutrición alterada), lo que también influye en la incidencia de obesidad y diabetes".
Según la última revisión elaborada por Puertas, en los "países occidentales entre un 20% y un 25% de la población trabaja a turnos". No se trata de eliminar esta organización de trabajo, ya que "tal y como está estructurada la vida no se pueden quitar, por ejemplo, las urgencias de los hospitales". Quizás, sí sería interesante "plantearse qué trabajadores nocturnos son más susceptibles (por predisposición genética) para establecer mecanismos de prevención como la promoción de un estilo de vida saludable, control de su peso, detección precoz y tratamiento de la prediabetes y la diabetes", concluyen los autores en su artículo.
**Publicado en "EL MUNDO"
Ya se tenían indicios sobre esta asociación, sobre todo con la obesidad y los riesgos cardiovasculares, pero "este es uno de los primeros trabajos que se basa en una cohorte tan amplia y con un seguimiento de muchos años", señala Francisco Javier Puertas, miembro de la Sociedad Española del Sueño y responsable de la Unidad del Sueño del Hospital Universitario de la Ribera (Valencia).
Frank Hu y su equipo de investigadores utilizaron los datos de dos encuestas de salud realizadas a las enfermeras en 1976 y en 1989. "Seguimos a 69.269 mujeres de la primera encuesta y a 107.915 de la segunda, todas sin diabetes, sin enfermedades cardiovasculares y sin cáncer". Del primer grupo, 6.165 desarrollaron diabetes tipo 2 y del segundo, 3.961.
Después de 20 años de seguimiento y relacionando los resultados con los turnos de noche que hacía cada enfermera, los autores de este trabajo observacional se dieron cuenta de que el riesgo de diabetes estaba muy relacionado con sus rotaciones nocturnas y esto se intensificaba a medida que pasaba el tiempo. "Comparado con las mujeres que no tenían turnos de noche, aquellas que lo mantenían entre uno o dos años, tenían un 5% más de riesgo; si tenían estos turnos durante 3-9 años, el porcentaje incrementaba a un 20% y hasta un 40% si las enfermeras se pasaban entre 10 y 19 años con estos turnos. Más de 20 años implicaba casi el 60% más de riesgo".
Como explica el especialista español al comentar este estudio, "sabemos, por modelos experimentales en adultos jóvenes, que la privación total o parcial del sueño después de una semana provoca un efecto parecido al de las personas con diabetes. Presentan problemas para absorber la glucosa, es decir, de alguna manera, genera estados prediabéticos". La cantidad y la calidad del sueño es fundamental para el correcto funcionamiento del sistema metabólico, agrega.
Como explica el experto, el descanso diurno es "poco reparador", ya que durante el día los parámetros biológicos tienen unas constantes naturales diferentes a las de la noche, en que el organismo se prepara para descansar. "Al cuerpo no se le puede engañar". En el trabajador nocturno se produce un desajuste de su ritmo "circadiano natural", lo que se traduce en una predisposición a la fatiga y la irritabilidad.
Aunque estos datos confirman una hipótesis anterior, los autores del estudio realizado en Boston reconocen que la asociación entre turnos de noche y diabetes era más débil si se tenían en cuenta otros factores como la nutrición. Generalmente, apunta el doctor Puertas, "los trabajadores nocturnos tienen menos actividad física y comen a deshoras (nutrición alterada), lo que también influye en la incidencia de obesidad y diabetes".
Según la última revisión elaborada por Puertas, en los "países occidentales entre un 20% y un 25% de la población trabaja a turnos". No se trata de eliminar esta organización de trabajo, ya que "tal y como está estructurada la vida no se pueden quitar, por ejemplo, las urgencias de los hospitales". Quizás, sí sería interesante "plantearse qué trabajadores nocturnos son más susceptibles (por predisposición genética) para establecer mecanismos de prevención como la promoción de un estilo de vida saludable, control de su peso, detección precoz y tratamiento de la prediabetes y la diabetes", concluyen los autores en su artículo.
**Publicado en "EL MUNDO"
Reusing pacemakers from deceased patients is safe and effective, study finds
Many heart patients in India are too poor to afford pacemakers. But a study has found that removing pacemakers from deceased Americans, resterilizing the devices and implanting them in Indian patients "is very safe and effective." Dr. Gaurav Kulkarni of Loyola University Medical Center is a co-author of the study, published online ahead of print in the American Journal of Cardiology. Kulkarni helped conduct the research before coming to Loyola while he was a medical student in India.
Fifty-three poor patients in Mumbai received pacemakers that had been donated by the families of deceased Americans. Following operations to reimplant the devices, all Indian patients were alive and doing well, researchers reported.
The Indian patients had severe heart rhythm disorders called complete heart block and sick sinus syndrome. Typically, the slightest physical exertion would leave them gasping for breath and exhausted. Without pacemakers, they likely would have died within weeks or months. But in India, a pacemaker costs $2,200 to $6,600, which is well beyond the means of many patients.
The pacemaker donations began as a philanthropic project. Physicians later decided to make a formal study of the safety and effectiveness of the donated devices. At every step of the study, patients gave informed consent. After receiving the reused pacemakers, they were followed for an average of nearly two years. There were no infections or other significant complications and no device failures. All but two patients reported marked improvement in their symptoms.
Of four patients who were previously employed, all were able to return to their manual jobs. Twenty-seven women said their symptoms had improved enough so they could resume household chores.
"Implantation of donated permanent pacemakers can not only save lives, but also improve quality of life of needy poor patients," researchers wrote.
Kulkarni added: "Without pacemakers, these patients would pretty much be forced to remain on confined rest, due to cardiac fatigue."
Kulkarni was born and raised in Mumbai, and at the time of the study, was a medical student at King Edward Memorial Hospital in Mumbai. He interviewed patients before and after they received pacemakers and collected data for the study. "There was a dramatic change in patients after they received their pacemakers," he said.
The Food and Drug Administration prohibits reusing pacemakers in the United States. But there is no prohibition against donating and reusing pacemakers in other countries.
Researchers reported that between January 2004 and January 2010, 121 pacemakers were removed and donated. (The devices were made by Medtronic, St. Jude Medical and Boston Scientific.) Sixty pacemakers were selected because they had a battery life greater than three years, but seven were discarded due to further decay in battery life. The remaining 53 pacemakers were rigorously cleaned and sterilized. They were sent to Holy Family Hospital in Mumbai, which serves all patients, regardless of income.
There have been previous studies of reused pacemakers. But only one previous study involved the reuse of pacemakers donated by families in the United States. That study included 12 patients in the Philippines.
The authors conclude that reusing pacemakers could "alleviate the burden of symptomatic bradyarrhythmia (abnormally slow heart rate) in impoverished nations around the world."
*Source: Loyola University Health System
Fifty-three poor patients in Mumbai received pacemakers that had been donated by the families of deceased Americans. Following operations to reimplant the devices, all Indian patients were alive and doing well, researchers reported.
The Indian patients had severe heart rhythm disorders called complete heart block and sick sinus syndrome. Typically, the slightest physical exertion would leave them gasping for breath and exhausted. Without pacemakers, they likely would have died within weeks or months. But in India, a pacemaker costs $2,200 to $6,600, which is well beyond the means of many patients.
The pacemaker donations began as a philanthropic project. Physicians later decided to make a formal study of the safety and effectiveness of the donated devices. At every step of the study, patients gave informed consent. After receiving the reused pacemakers, they were followed for an average of nearly two years. There were no infections or other significant complications and no device failures. All but two patients reported marked improvement in their symptoms.
Of four patients who were previously employed, all were able to return to their manual jobs. Twenty-seven women said their symptoms had improved enough so they could resume household chores.
"Implantation of donated permanent pacemakers can not only save lives, but also improve quality of life of needy poor patients," researchers wrote.
Kulkarni added: "Without pacemakers, these patients would pretty much be forced to remain on confined rest, due to cardiac fatigue."
Kulkarni was born and raised in Mumbai, and at the time of the study, was a medical student at King Edward Memorial Hospital in Mumbai. He interviewed patients before and after they received pacemakers and collected data for the study. "There was a dramatic change in patients after they received their pacemakers," he said.
The Food and Drug Administration prohibits reusing pacemakers in the United States. But there is no prohibition against donating and reusing pacemakers in other countries.
Researchers reported that between January 2004 and January 2010, 121 pacemakers were removed and donated. (The devices were made by Medtronic, St. Jude Medical and Boston Scientific.) Sixty pacemakers were selected because they had a battery life greater than three years, but seven were discarded due to further decay in battery life. The remaining 53 pacemakers were rigorously cleaned and sterilized. They were sent to Holy Family Hospital in Mumbai, which serves all patients, regardless of income.
There have been previous studies of reused pacemakers. But only one previous study involved the reuse of pacemakers donated by families in the United States. That study included 12 patients in the Philippines.
The authors conclude that reusing pacemakers could "alleviate the burden of symptomatic bradyarrhythmia (abnormally slow heart rate) in impoverished nations around the world."
*Source: Loyola University Health System
El dr Fco José Ruza a ABC: "Buscamos un menú musical para cada trastorno infantil"
Francisco José Ruza pertenece a una generación de médicos pioneros. Formó parte de la primera promoción MIR que hubo en España, asistió al nacimiento del Hospital Infantil La Paz de Madrid y dirigió una de las primeras unidades de cuidados intensivos infantil del país. En este hospital ha pasado toda su carrera profesional, cuarenta años en los que los cuidados críticos de los niños han evolucionado a golpe de técnica. Ahora Ruza, recién elegido miembro de la Academia de Medicina de Galicia, ha cambiado la asistencia por la docencia y la investigación.
—¿En qué proyecto trabaja?
—En líneas de investigación humanistas, como complemento a la medicina técnica. Trabajamos mucho en musicoterapia. En la unidad de cuidados intensivos de La Paz hemos comprobado cómo la música ayuda a bebés de menos de seis meses. La mejoría se observa incluso en niños sedados. —¿Cuál es la sintonía que mejor funciona y para qué problemas?
—Aún no lo sabemos. Queremos averiguar cual es la música más adecuada para cada una de las patologías, buscamos un menú musical para cada trastorno. Ya sabemos que Mozart tranquiliza a los niños. Y que cuando están bajos de tono, funciona la música estimulante. En directo y a pie de cuna hemos visto cosas fantásticas como que los niños adaptan sus latidos al ritmo musical.
—Hoy las UCI son pura sofisticación. ¿Basta esta tecnología para saber lo que le ocurre a un niño?
—La pediatría es la especialidad que tiene la información más limitada. No es directa. Es la madre o el padre los que nos dicen lo que sienten los niños. Por eso, el punto fuerte siempre ha sido la exploración clínica. La exploración, más la tecnología que nos indica cómo evolucionan los órganos.
—¿El pediatra no debe tener un instinto especial para comunicarse con los niños?
—Desde luego. Hoy hay tal cantidad de información sobre parámetros biológicos objetivos que bastaría con tener esos datos para hacer un diagnóstico y esa es una tentación peligrosa. Nunca se debe perder el contacto con el niño. Es algo que me preocupa e insisto mucho a mis estudiantes.
—¿Le preocupa que Internet se haya convertido en el «pediatra» al que acuden los padres?
—Sí, unas veces orienta y otras, las más, desorienta a los padres. Les agobia y les hace creer situaciones fuera del contexto que es su hijo.
—¿Cuál es el principal mal que padecen hoy los niños españoles?
—Desde el punto de vista biológico, probablemente sea la obesidad y desde una mirada psicológica, la desorientación educativa. La sobreprotección y el excesivo consentimiento que crea auténticos tiranos.Tan malo es asfixiar a un niño para que no desarrolle su propia personalidad como dejarle libertad total.
—En época de recortes una tentación es sustituir a pediatras por médicos de adultos. ¿Se resentirá la atención infantil?
—Sería un grave error y un deterioro de la asistencia. La sociedad está concienciada de que al niño le debe ver el pediatra porque le da garantías de calidad. No aceptaría una involución en el sistema.
—¿En qué proyecto trabaja?
—En líneas de investigación humanistas, como complemento a la medicina técnica. Trabajamos mucho en musicoterapia. En la unidad de cuidados intensivos de La Paz hemos comprobado cómo la música ayuda a bebés de menos de seis meses. La mejoría se observa incluso en niños sedados. —¿Cuál es la sintonía que mejor funciona y para qué problemas?
—Aún no lo sabemos. Queremos averiguar cual es la música más adecuada para cada una de las patologías, buscamos un menú musical para cada trastorno. Ya sabemos que Mozart tranquiliza a los niños. Y que cuando están bajos de tono, funciona la música estimulante. En directo y a pie de cuna hemos visto cosas fantásticas como que los niños adaptan sus latidos al ritmo musical.
—Hoy las UCI son pura sofisticación. ¿Basta esta tecnología para saber lo que le ocurre a un niño?
—La pediatría es la especialidad que tiene la información más limitada. No es directa. Es la madre o el padre los que nos dicen lo que sienten los niños. Por eso, el punto fuerte siempre ha sido la exploración clínica. La exploración, más la tecnología que nos indica cómo evolucionan los órganos.
—¿El pediatra no debe tener un instinto especial para comunicarse con los niños?
—Desde luego. Hoy hay tal cantidad de información sobre parámetros biológicos objetivos que bastaría con tener esos datos para hacer un diagnóstico y esa es una tentación peligrosa. Nunca se debe perder el contacto con el niño. Es algo que me preocupa e insisto mucho a mis estudiantes.
—¿Le preocupa que Internet se haya convertido en el «pediatra» al que acuden los padres?
—Sí, unas veces orienta y otras, las más, desorienta a los padres. Les agobia y les hace creer situaciones fuera del contexto que es su hijo.
—¿Cuál es el principal mal que padecen hoy los niños españoles?
—Desde el punto de vista biológico, probablemente sea la obesidad y desde una mirada psicológica, la desorientación educativa. La sobreprotección y el excesivo consentimiento que crea auténticos tiranos.Tan malo es asfixiar a un niño para que no desarrolle su propia personalidad como dejarle libertad total.
—En época de recortes una tentación es sustituir a pediatras por médicos de adultos. ¿Se resentirá la atención infantil?
—Sería un grave error y un deterioro de la asistencia. La sociedad está concienciada de que al niño le debe ver el pediatra porque le da garantías de calidad. No aceptaría una involución en el sistema.
**Publicado en "ABC"
Poorly contracting uterus in diabetic women increases risk of caesarean birth
Researchers at the University of Liverpool have found that the strength of uterine contractions in diabetic pregnant women is significantly weaker than in non-diabetic women, increasing the risk of emergency caesarean birth. In the past 10 years the prevalence of births complicated by diabetes has increased by approximately 50%. There has, however, been very little research undertaken to understand why only a quarter will have a normal vaginal delivery.
Scientists at the University, working with the Liverpool Women's Hospital, studied more than 100 biopsies of the uterus from pregnant women with and without diabetes. They found that contractions in women who had the disease were not as strong as those in non-diabetic women. To understand why this happens the team looked at possible differences in the changes in calcium within the muscle cells, as this is an essential component of uterine contractions.
Calcium levels in the uterus should rise to allow the muscle to contract effectively. Researchers found, however, that in women with diabetes, calcium levels are significantly reduced. Further investigation revealed that the channels in the cell membrane, that are necessary for calcium to enter the cells, were also reduced. This suggests why the uterus may not contract as strongly as it should in women with diabetes.
Uterus tissue in diabetic women also failed to reach the same levels of contractility as in non-diabetic women when stimulated with the drug oxytocin, a commonly used treatment for women experiencing difficult births. The research suggests why so many pregnancies in diabetic women result in an emergency caesarean.
Professor Sue Wray, from the University's Institute of Translational Medicine, said: "In the UK approximately 35,000 pregnant women per year have diabetes and some women develop the condition during pregnancy, a condition called gestational diabetes. We know that more than 60% of these women will need a caesarean section in order to deliver a baby successfully.
"These major operations increase the risk of complications and infection, as well as excessive bleeding and haemorrhage. Up until now we have not known why diabetic women suffer such complicated births, but it is important that more work is done in this field to prevent the further increase in emergency caesarean sections.
"Our work shows that calcium in inhibited from entering the muscle cells. This, together with evidence of reduced overall muscle mass, contributes to a poorly contracting uterus in women with diabetes. Future studies to help diabetic women should now focus on why the condition causes these changes in the first instance and if there is any way to stop it from happening."
The research, supported by Diabetes UK, is published in the journal Diabetologia.
*Source: University of Liverpool
Scientists at the University, working with the Liverpool Women's Hospital, studied more than 100 biopsies of the uterus from pregnant women with and without diabetes. They found that contractions in women who had the disease were not as strong as those in non-diabetic women. To understand why this happens the team looked at possible differences in the changes in calcium within the muscle cells, as this is an essential component of uterine contractions.
Calcium levels in the uterus should rise to allow the muscle to contract effectively. Researchers found, however, that in women with diabetes, calcium levels are significantly reduced. Further investigation revealed that the channels in the cell membrane, that are necessary for calcium to enter the cells, were also reduced. This suggests why the uterus may not contract as strongly as it should in women with diabetes.
Uterus tissue in diabetic women also failed to reach the same levels of contractility as in non-diabetic women when stimulated with the drug oxytocin, a commonly used treatment for women experiencing difficult births. The research suggests why so many pregnancies in diabetic women result in an emergency caesarean.
Professor Sue Wray, from the University's Institute of Translational Medicine, said: "In the UK approximately 35,000 pregnant women per year have diabetes and some women develop the condition during pregnancy, a condition called gestational diabetes. We know that more than 60% of these women will need a caesarean section in order to deliver a baby successfully.
"These major operations increase the risk of complications and infection, as well as excessive bleeding and haemorrhage. Up until now we have not known why diabetic women suffer such complicated births, but it is important that more work is done in this field to prevent the further increase in emergency caesarean sections.
"Our work shows that calcium in inhibited from entering the muscle cells. This, together with evidence of reduced overall muscle mass, contributes to a poorly contracting uterus in women with diabetes. Future studies to help diabetic women should now focus on why the condition causes these changes in the first instance and if there is any way to stop it from happening."
The research, supported by Diabetes UK, is published in the journal Diabetologia.
*Source: University of Liverpool
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